95 results on '"Zwaenepoel K"'
Search Results
2. CD70: An emerging target in cancer immunotherapy
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Jacobs, J., Deschoolmeester, V., Zwaenepoel, K., Rolfo, C., Silence, K., Rottey, S., Lardon, F., Smits, E., and Pauwels, P.
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- 2015
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3. Results of a first panTRK IHC ringtrial
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De Winne, K., primary, Sorber, L., additional, Lambin, S., additional, Keulen, L., additional, Broeckx, G., additional, Pauwels, P., additional, and Zwaenepoel, K., additional
- Published
- 2019
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4. A stitch in time saves nine External quality assessment rounds demonstrate improved quality of biomarker analysis in lung cancer
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Keppens , C., Tack , V., 't Hart , N., Tembuyser , L., Ryska , A., Pauwels , P., Zwaenepoel , K., Schuuring , E., Cabillic , F., Tornillo , L., Warth , A., Weichert , W., Dequeker , E., Lukas , B., Sofie , D., Keith , M., Erik , T., Catholic University of Leuven ( KU Leuven ), University of Antwerp ( UA ), Antwerp University Hospital [Edegem], University Medical Center Groningen [Groningen] ( UMCG ), CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer ( NuMeCan ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), University of Basel ( Unibas ), Heidelberg University Hospital [Heidelberg], Technical University of Munich ( TUM ), and University Hospital Basel [Basel]
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Targeted therapy ,Molecular pathology ,Non-small cell lung cancer ,[ SDV ] Life Sciences [q-bio] ,Biomarker analysis ,External quality assessment - Abstract
International audience; Biomarker analysis has become routine practice in the treatment of non-small cell lung cancer (NSCLC). To ensure high quality testing, participation to external quality assessment (EQA) schemes is essential. This article provides a longitudinal overview of the EQA performance for EGFR, ALK, and ROS1 analyses in NSCLC between 2012 and 2015. The four scheme years were organized by the European Society of Pathology according to the ISO 17043 standard. Participants were asked to analyze the provided tissue using their routine procedures. Analysis scores improved for individual laboratories upon participation to more EQA schemes, except for ROS1 immunohistochemistry (IHC). For EGFR analysis, scheme error rates were 18.8%, 14.1% and 7.5% in 2013, 2014 and 2015 respectively. For ALK testing, error rates decreased between 2012 and 2015 by 5.2%, 3.2% and 11.8% for the fluorescence in situ hybridization (FISH), FISH digital, and IHC subschemes, respectively. In contrast, for ROS1 error rates increased between 2014 and 2015 for FISH and IHC by 3.2% and 9.3%. Technical failures decreased over the years for all three markers. Results show that EQA contributes to an ameliorated performance for most predictive biomarkers in NSCLC. Room for improvement is still present, especially for ROS1 analysis. © Keppens et al.
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- 2018
5. Detection of mutations and copy number alterations in circulating DNA from pancreatic neuroendocrine tumor patients
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Boons, G., primary, Op de Beeck, K., additional, Vandamme, T., additional, Beyens, M., additional, Roeyen, G., additional, Janssens, K., additional, Zwaenepoel, K., additional, van Camp, G., additional, and Peeters, M., additional
- Published
- 2018
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6. PO-306 Targeting CD70-positive cancer associated fibroblasts to tackle the immune suppressive tumour microenvironment in colorectal cancer
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Jacobs, J., primary, Deschoolmeester, V., additional, Zwaenepoel, K., additional, Flieswasser, T., additional, Peeters, M., additional, Dewever, O., additional, Lardon, F., additional, Siozopoulou, V., additional, Smits, E., additional, and Pauwels, P., additional
- Published
- 2018
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7. PO-429 Identification of the right immunostimulatory chemotherapeutic partner for anti-CD70 immunotherapy in non-small cell lung cancer
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Flieswasser, T., primary, Loenhout, J. Van, additional, Zwaenepoel, K., additional, Rolfo, C., additional, Lardon, F., additional, Smits, E., additional, Jacobs, J., additional, and Pauwels, P., additional
- Published
- 2018
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8. PO-458 A multicenter study to assess EGFR mutational status in plasma: focus on an optimisedworkflow for liquid biopsy in a clinical setting
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Sorber, L., primary, Zwaenepoel, K., additional, Demedts, I., additional, Pieters, T., additional, Germonpré, P., additional, Derijcke, S., additional, Deschepper, K., additional, Meerbeeck, J. Van, additional, Rolfo, C., additional, and Pauwels, P., additional
- Published
- 2018
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9. Liquid biopsies in lung cancer: The new ambrosia of researchers
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Rolfo, C, Castiglia, M, Hong, D, Alessandro, R, Mertens, I, Baggerman, G, Zwaenepoel, K, Gil-Bazo, I, Passiglia, F, Carreca, AP, Taverna, S, Vento, R, Peeters, M, Russo, A, Pauwels, P, Rolfo, C, Castiglia, M, Hong, D, Alessandro, R, Mertens, I, Baggerman, G, Zwaenepoel, K, Gil-Bazo, I, Passiglia, F, Carreca, AP, Taverna, S, Vento, R, Peeter, Russo, A, and Pauwels, P
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Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Pleural effusion ,Settore MED/06 - Oncologia Medica ,Biopsy ,exosomes ,circulating tumor cells ,Circulating tumor cell ,Settore BIO/13 - Biologia Applicata ,Internal medicine ,Settore BIO/10 - Biochimica ,Genetics ,medicine ,Biomarkers, Tumor ,exosome ,Animals ,Humans ,cancer ,Biomarker discovery ,Liquid biopsy ,Lung cancer ,Biology ,liquid biopsy ,business.industry ,Physics ,Cancer ,DNA, Neoplasm ,medicine.disease ,Neoplastic Cells, Circulating ,Chemistry ,Immunology ,Biomarker (medicine) ,Human medicine ,Personalized medicine ,business - Abstract
In the last decades the approach to cancer patient management has been deeply revolutionized. We are moving from a "one-fits-all" strategy to the "personalized medicine" based on the molecular characterization of the tumor. In this new era it is becoming more and more clear that the monitoring of the disease is fundamental for the success of the treatment, thus there is the need of new biomarker discovery. More precisely in the last years the scientific community has started to use the term "liquid biopsy". A liquid biopsy is a liquid biomarker that can be easily isolated from many body fluids (blood, saliva, urine, ascites, pleural effusion, etc.) and, as well as a tissue biopsy, a representative of the tissue from which it is spread. In this review we will focus our attention on circulating tumor cells, circulating tumor DNA, exosomes and secretomes with the aim to underlie their usefulness and potential application in a clinical setting for lung cancer patient management. (C) 2014 Elsevier B.V. All rights reserved.
- Published
- 2014
10. 36P - Results of a first panTRK IHC ringtrial
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De Winne, K., Sorber, L., Lambin, S., Keulen, L., Broeckx, G., Pauwels, P., and Zwaenepoel, K.
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- 2019
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11. Circulating cell-free nucleic acids and platelets as a liquid biopsy in the provision of personalized therapy for lung cancer patients
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Sorber, L., primary, Zwaenepoel, K., additional, Deschoolmeester, V., additional, Van Schil, P.E.Y., additional, Van Meerbeeck, J., additional, Lardon, F., additional, Rolfo, C., additional, and Pauwels, P., additional
- Published
- 2017
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12. 1332P - Detection of mutations and copy number alterations in circulating DNA from pancreatic neuroendocrine tumor patients
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Boons, G., Op de Beeck, K., Vandamme, T., Beyens, M., Roeyen, G., Janssens, K., Zwaenepoel, K., van Camp, G., and Peeters, M.
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- 2018
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13. 2880 Immunohistochemical analysis of CD70 expression in 95 cases of squamous cell carcinoma of the head and neck: Correlation with clinicopathological variables and identification of a novel therapeutic target
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De Meulenaere, A., primary, Vermassen, T., additional, Aspeslagh, S., additional, Deron, P., additional, Duprez, F., additional, Silence, K., additional, Jacobs, J., additional, Zwaenepoel, K., additional, Pauwels, P., additional, Rottey, S., additional, and Ferdinande, L., additional
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- 2015
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14. 200 The influence of different cMET and EGFR backgrounds on the cytotoxicity of cMET and EGFR small molecule inhibitors in vitro
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van der Steen, N., primary, Zwaenepoel, K., additional, Rolfo, C., additional, Giovannetti, E., additional, Castiglia, M., additional, Deschoolmeester, V., additional, Carreca, A.P., additional, Germonpre, P., additional, and Pauwels, P., additional
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- 2014
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15. 347 Can a link between the EGFR and cMET pathway in non-small cell lung cancer explain resistance against targeted therapies and open new therapeutic opportunities?
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van der Steen, N., primary, van der Steen, K., additional, Zwaenepoel, K., additional, Giovannetti, E., additional, Castiglia, M., additional, Carreca, A.P., additional, Pauwels, P., additional, and Rolfo, C., additional
- Published
- 2014
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16. 108 CD70 (TNFSF7), a receptor involved in acute immune modulation of viral infection, is frequently overexpressed in solid and hematological malignancies
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Jacobs, J., primary, Zwaenepoel, K., additional, Aftimos, P., additional, Rolfo, C., additional, Rottey, S., additional, de Lendonck, L. Ysebrant, additional, Silence, K., additional, Awada, A., additional, Thibault, A., additional, and Pauwels, P., additional
- Published
- 2014
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17. Importance of External Quality Assessement in Immuno-Oncology
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Dequeker, E., primary, Tembuyser, L., additional, Tack, V., additional, Zwaenepoel, K., additional, Pauwels, P., additional, and Thunnissen, E., additional
- Published
- 2014
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18. 137IN - Importance of External Quality Assessement in Immuno-Oncology
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Dequeker, E., Tembuyser, L., Tack, V., Zwaenepoel, K., Pauwels, P., and Thunnissen, E.
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- 2014
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19. Diversity in genomic organisation, developmental regulation and distribution of the murine PR72/B' subunits of protein phosphatase 2A
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Janssens Veerle, Goris Jozef, Louis Justin V, and Zwaenepoel Karen
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Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background Protein phosphatase 2A (PP2A) is a serine/threonine-specific phosphatase displaying vital functions in growth and development through its role in various signalling pathways. PP2A holoenzymes comprise a core dimer composed of a catalytic C and a structural A subunit, which can associate with a variable B-type subunit. The importance of the B-type subunits for PP2A regulation cannot be overestimated as they determine holoenzyme localisation, activity and substrate specificity. Three B-type subunit families have been identified: PR55/B, PR61/B' and PR72/B", of which the latter is currently the least characterised. Results We deduced the sequences and genomic organisation of the different murine PR72/B" isoforms: three genes encode nine isoforms, five of which are abundantly expressed and give rise to genuine PP2A subunits. Thereby, one novel subunit was identified. Using Northern blotting, we examined the tissue-specific and developmental expression of these subunits. All subunits are highly expressed in heart, suggesting an important cardiac function. Immunohistochemical analysis revealed a striated expression pattern of PR72 and PR130 in heart and skeletal muscle, but not in bladder smooth muscle. The subcellular localisation and cell cycle regulatory ability of several PR72/B" isoforms were determined, demonstrating differences as well as similarities. Conclusion In contrast to PR55/B and PR61/B', the PR72/B" family seems evolutionary more divergent, as only two of the murine genes have a human orthologue. We have integrated these results in a more consistent nomenclature of both human and murine PR72/B" genes and their transcripts/proteins. Our results provide a platform for the future generation of PR72/B" knockout mice.
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- 2008
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20. 36P Results of a first panTRK IHC ringtrial.
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Winne, K De, Sorber, L, Lambin, S, Keulen, L, Broeckx, G, Pauwels, P, and Zwaenepoel, K
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- *
GENE fusion , *PROTEIN-tyrosine kinases , *UNIVERSITY hospitals , *CLONE cells - Abstract
Background Because of the limited experience with tyrosine kinase receptor (TRK) gene fusion, a Belgian ring trial for TRK immunohistochemistry (IHC) staining was organised by the pathology department of Antwerp University Hospital. The trial was conducted between January and July 2019 with a total of 9 participating laboratories and aimed to harmonize pan-TRK IHC staining protocols and pan-TRK IHC interpretation. Methods The first and last slides of six selected cases were stained for TRK using the VENTANA pan-TRK Assay (clone EPR17341) on the Benchmark Ultra platform. Each participating laboratory received two unstained slides and was asked to return one TRK–stained slide per case and to report the protocol used and their interpretation. One site participated with two different protocols. The stained slides were evaluated by two designated pathologists. The results of a comparative study evaluating the IHC interpretations from the in-house pathologists of the different laboratories and those obtained from the trial-designated pathologists were communicated to the participating laboratories. Results Two different clones were used during the ring trial: A7H6R (Cell Signaling) and EPR17341 (Abcam/Ventana). The VENTANA pan-TRK Assay (clone EPR17341) on the Benchmark Ultra platform was most popular and used by 40% of the labs. The remaining in-house protocols used EPR17341 in its concentrated form (abcam) or A7H6R (Cell Signaling). Overall, 7 protocols achieved a sufficient performance mark and 3 labs were advised to further optimise the protocol. Interpretation of panTRK IHC proofed to be challenging in cases with physiological TRK expression. In addition, depending on the NTRK fusion partner, the staining can vary strongly in both intensity and staining pattern. Conclusions To our knowledge, this is the first panTRK IHC ring trial. According to our results, the EPR17341 and A7H6R clones are both highly recommendable antibodies for panTRK IHC. Labs using the Ventana ready-to-use system based on the EPR17341 clone and using the recommended protocol settings scored best. However, given some small optimisation, all labs scored well on the technical staining and the succeeding evaluation. Legal entity responsible for the study Antwerp University Hospital. Funding Bayer. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]
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- 2019
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21. Corrigendum to 'Liquid biopsies in lung cancer: The new ambrosia of researchers' [Biochem. Biophys. Act. 1846(2014) 539–546]
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Antonio Russo, Francesco Passiglia, Christian Rolfo, Geert Baggerman, Inge Mertens, Marta Castiglia, Daniele Santini, Anna Paola Carreca, Patrick Pauwels, Karen Zwaenepoel, Simona Taverna, Renza Vento, Ignacio Gil-Bazo, Riccardo Alessandro, David S. Hong, Marc Peeters, Rolfo C., Castiglia M., Hong D., Alessandro R., Mertens I., Baggerman G., Zwaenepoel K., Gil-Bazo I., Passiglia F., Carreca A.P., Taverna S., Vento R., Santini D., Peeters M., Russo A., and Pauwels P.
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University campus ,Cancer Research ,Oncology ,F-Center ,Settore MED/06 - Oncologia Medica ,Genetics ,The name of the author Daniele Santini was inadvertently omitted from the author line. The correct author line is above ,Library science ,University hospital - Abstract
a Phase I — Early Clinical Trials Unit, Oncology Department, Antwerp University Hospital, Wilrijkstraat 10, Edegem 2650, Belgium b Molecular Pathology Unit, Pathology Department, Antwerp University Hospital, Wilrijkstraat 10, Edegem 2650, Belgium c Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Via Liborio Giuffre 5, Palermo 90127, Italy d Department of Investigational Cancer Therapeutics (Phase I Program), The University of Texas MD Anderson Cancer Center, Holcombe Blvd 1400, Unit 455, Houston 77030, USA e Department of Biopathology and Medical and Forensic Biotechnologies, Section of Biology and Genetics, University of Palermo, Via Divisi 81-85, 90133 Palermo, Italy f Center for Proteomics, VITO, Boeretang 200, Mol BE-2400, Belgium g Lung Cancer Unit, Department of Oncology, Clinica Universidad de Navarra, Avenida Pio XII 36, Pamplona 31008, Spain h Laboratory of Biochemistry, Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Polyclinic, University of Palermo, Viale delle Scienze, Ed. 13, 90128 Palermo, Italy i Medical Oncology Department, University Campus Bio-Medico, Rome, Italy j Oncology Department, Antwerp University Hospital, Wilrijkstraat 10, Edegem 2650, Belgium k Antwerp University, Groenenborgerlaan 171, Antwerpen 2020, Belgium
- Published
- 2015
22. External Quality Assessment on Molecular Tumor Profiling with Circulating Tumor DNA-Based Methodologies Routinely Used in Clinical Pathology within the COIN Consortium.
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van der Leest P, Rozendal P, Hinrichs J, van Noesel CJM, Zwaenepoel K, Deiman B, Huijsmans CJJ, van Eijk R, Speel EJM, van Haastert RJ, Ligtenberg MJL, van Schaik RHN, Jansen MPHM, Dubbink HJ, de Leng WW, Leers MPG, Tamminga M, van den Broek D, van Kempen LC, and Schuuring E
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- Humans, Mutation, Neoplasms genetics, Neoplasms blood, Proto-Oncogene Proteins p21(ras) genetics, ErbB Receptors genetics, ErbB Receptors blood, Proto-Oncogene Proteins B-raf genetics, Netherlands, Circulating Tumor DNA blood, Circulating Tumor DNA genetics
- Abstract
Background: Identification of tumor-derived variants in circulating tumor DNA (ctDNA) has potential as a sensitive and reliable surrogate for tumor tissue-based routine diagnostic testing. However, variations in pre(analytical) procedures affect the efficiency of ctDNA recovery. Here, an external quality assessment (EQA) was performed to determine the performance of ctDNA mutation detection work flows that are used in current diagnostic settings across laboratories within the Dutch COIN consortium (ctDNA on the road to implementation in The Netherlands)., Methods: Aliquots of 3 high-volume diagnostic leukapheresis (DLA) plasma samples and 3 artificial reference plasma samples with predetermined mutations were distributed among 16 Dutch laboratories. Participating laboratories were requested to perform ctDNA analysis for BRAF exon 15, EGFR exon 18-21, and KRAS exon 2-3 using their regular circulating cell-free DNA (ccfDNA) analysis work flow. Laboratories were assessed based on adherence to the study protocol, overall detection rate, and overall genotyping performance., Results: A broad range of preanalytical conditions (e.g., plasma volume, elution volume, and extraction methods) and analytical methodologies (e.g., droplet digital PCR [ddPCR], small-panel PCR assays, and next-generation sequencing [NGS]) were used. Six laboratories (38%) had a performance score of >0.90; all other laboratories scored between 0.26 and 0.80. Although 13 laboratories (81%) reached a 100% overall detection rate, the therapeutically relevant EGFR p.(S752_I759del) (69%), EGFR p.(N771_H773dup) (50%), and KRAS p.(G12C) (48%) mutations were frequently not genotyped accurately., Conclusions: Divergent (pre)analytical protocols could lead to discrepant clinical outcomes when using the same plasma samples. Standardization of (pre)analytical work flows can facilitate the implementation of reproducible liquid biopsy testing in the clinical routine., (© Association for Diagnostics & Laboratory Medicine 2024.)
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- 2024
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23. Singlet oxygen-based photoelectrochemical detection of single-point mutations in the KRAS oncogene.
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Daems E, Bassini S, Mariën L, Op de Beeck H, Stratulat A, Zwaenepoel K, Vandamme T, Op de Beeck K, Koljenović S, Peeters M, Van Camp G, and De Wael K
- Subjects
- Humans, Proto-Oncogene Proteins p21(ras) genetics, Singlet Oxygen, ras Proteins genetics, DNA Mutational Analysis methods, Mutation, Oncogenes, Point Mutation, Biosensing Techniques
- Abstract
Single nucleotide point mutations in the KRAS oncogene occur frequently in human cancers, rendering them intriguing targets for diagnosis, early detection and personalized treatment. Current detection methods are based on polymerase chain reaction, sometimes combined with next-generation sequencing, which can be expensive, complex and have limited availability. Here, we propose a novel singlet oxygen (
1 O2 )-based photoelectrochemical detection methodology for single-point mutations, using KRAS mutations as a case study. This detection method combines the use of a sandwich assay, magnetic beads and robust chemical photosensitizers, that need only air and light to produce1 O2 , to ensure high specificity and sensitivity. We demonstrate that hybridization of the sandwich hybrid at high temperatures enables discrimination between mutated and wild-type sequences with a detection rate of up to 93.9%. Additionally, the presence of background DNA sequences derived from human cell-line DNA, not containing the mutation of interest, did not result in a signal, highlighting the specificity of the methodology. A limit of detection as low as 112 pM (1.25 ng/mL) was achieved without employing any amplification techniques. The developed1 O2 -based photoelectrochemical methodology exhibits unique features, including rapidity, ease of use, and affordability, highlighting its immense potential in the field of nucleic acid-based diagnostics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)- Published
- 2024
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24. IL-15-secreting CAR natural killer cells directed toward the pan-cancer target CD70 eliminate both cancer cells and cancer-associated fibroblasts.
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Van den Eynde A, Gehrcken L, Verhezen T, Lau HW, Hermans C, Lambrechts H, Flieswasser T, Quatannens D, Roex G, Zwaenepoel K, Marcq E, Joye P, Cardenas De La Hoz E, Deben C, Gasparini A, Montay-Gruel P, Le Compte M, Lion E, Lardon F, Van Laere S, Siozopoulou V, Campillo-Davo D, De Waele J, Pauwels P, Jacobs J, Smits E, and Van Audenaerde JRM
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- Humans, Animals, Mice, Cytotoxicity, Immunologic, Interleukin-15 metabolism, Cell Line, Tumor, Killer Cells, Natural, Immunotherapy, Adoptive methods, Cytokines metabolism, CD27 Ligand, Cancer-Associated Fibroblasts, Lymphoma metabolism
- Abstract
Background: It remains challenging to obtain positive outcomes with chimeric antigen receptor (CAR)-engineered cell therapies in solid malignancies, like colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC). A major obstacle is the lack of targetable surface antigens that are not shared by healthy tissues. CD70 emerges as interesting target, due to its stringent expression pattern in healthy tissue and its apparent role in tumor progression in a considerable amount of malignancies. Moreover, CD70 is also expressed on cancer-associated fibroblasts (CAFs), another roadblock for treatment efficacy in CRC and PDAC. We explored the therapeutic potential of CD70 as target for CAR natural killer (NK) cell therapy in CRC, PDAC, focusing on tumor cells and CAFs, and lymphoma., Methods: RNA-seq data and immunohistochemical analysis of patient samples were used to explore CD70 expression in CRC and PDAC patients. In addition, CD70-targeting CAR NK cells were developed to assess cytotoxic activity against CD70
+ tumor cells and CAFs, and the effect of cytokine stimulation on their efficacy was evaluated. The in vitro functionality of CD70-CAR NK cells was investigated against a panel of tumor and CAF cell lines with varying CD70 expression. Lymphoma-bearing mice were used to validate in vivo potency of CD70-CAR NK cells. Lastly, to consider patient variability, CD70-CAR NK cells were tested on patient-derived organoids containing CAFs., Results: In this study, we identified CD70 as a target for tumor cells and CAFs in CRC and PDAC patients. Functional evaluation of CD70-directed CAR NK cells indicated that IL-15 stimulation is essential to obtain effective elimination of CD70+ tumor cells and CAFs, and to improve tumor burden and survival of mice bearing CD70+ tumors. Mechanistically, IL-15 stimulation resulted in improved potency of CD70-CAR NK cells by upregulating CAR expression and increasing secretion of pro-inflammatory cytokines, in a mainly autocrine or intracellular manner., Conclusions: We disclose CD70 as an attractive target both in hematological and solid tumors. IL-15 armored CAR NK cells act as potent effectors to eliminate these CD70+ cells. They can target both tumor cells and CAFs in patients with CRC and PDAC, and potentially other desmoplastic solid tumors., (© 2024. The Author(s).)- Published
- 2024
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25. Phase II Trial Assessing the Repeatability and Tumor Uptake of [ 68 Ga]Ga-HER2 Single-Domain Antibody PET/CT in Patients with Breast Carcinoma.
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Gondry O, Caveliers V, Xavier C, Raes L, Vanhoeij M, Verfaillie G, Fontaine C, Glorieus K, De Grève J, Joris S, Luyten I, Zwaenepoel K, Vandenbroucke F, Waelput W, Thyparambil S, Vaneycken I, Cousaert J, Bourgeois S, Devoogdt N, Goethals L, Everaert H, De Geeter F, Lahoutte T, and Keyaerts M
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- Humans, Female, Positron Emission Tomography Computed Tomography methods, Gallium Radioisotopes, Fluorodeoxyglucose F18, Positron-Emission Tomography, Single-Domain Antibodies metabolism, Breast Neoplasms metabolism
- Abstract
Human epidermal growth factor receptor 2 (HER2) status is used for decision-making in breast carcinoma treatment. The status is obtained through immunohistochemistry or in situ hybridization. These two methods have the disadvantage of necessitating tissue sampling, which is prone to error due to tumor heterogeneity or interobserver variability. Whole-body imaging might be a solution to map HER2 expression throughout the body. Methods: Twenty patients with locally advanced or metastatic breast carcinoma (5 HER2-positive and 15 HER2-negative patients) were included in this phase II trial to assess the repeatability of uptake quantification and the extended safety of the [
68 Ga]Ga-NOTA-anti-HER2 single-domain antibody (sdAb). The tracer was injected, followed by a PET/CT scan at 90 min. Within 8 d, the procedure was repeated. Blood samples were taken for antidrug antibody (ADA) assessment and liquid biopsies. On available tissues, immunohistochemistry, in situ hybridization, and mass spectrometry were performed to determine the correlation of HER2 status with uptake values measured on PET. If relevant preexisting [18 F]FDG PET/CT images were available (performed as standard of care), a comparison was made. Results: With a repeatability coefficient of 21.8%, this imaging technique was repeatable. No clear correlation between PET/CT uptake values and pathology could be established, as even patients with low levels of HER2 expression showed moderate to high uptake. Comparison with [18 F]FDG PET/CT in 16 patients demonstrated that in 7 patients, [68 Ga]Ga-NOTA-anti-HER2 shows interlesional heterogeneity within the same patient, and [18 F]FDG uptake did not show the same heterogeneous uptake in all patients. In some patients, the extent of disease was clearer with the [68 Ga]Ga-NOTA-anti-HER2-sdAb. Sixteen adverse events were reported but all without a clear relationship to the tracer. Three patients with preexisting ADAs did not show adverse reactions. No new ADAs developed. Conclusion: [68 Ga]Ga-NOTA-anti-HER2-sdAb PET/CT imaging shows similar repeatability to [18 F]FDG. It is safe for clinical use. There is tracer uptake in cancer lesions, even in patients previously determined to be HER2-low or -negative. The tracer shows potential in the assessment of interlesional heterogeneity of HER2 expression. In a subset of patients, [68 Ga]Ga-NOTA-anti-HER2-sdAb uptake was seen in lesions with no or low [18 F]FDG uptake. These findings support further clinical development of [68 Ga]Ga-NOTA-anti-HER2-sdAb as a PET/CT tracer in breast cancer patients., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2024
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26. Belgian Recommendations for Analytical Verification and Validation of Immunohistochemical Tests in Laboratories of Anatomic Pathology.
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Verbeke H, Van Hecke D, Bauraing C, Dierick AM, Colleye O, Dalle I, Dewachter K, Guiot Y, Lequeu R, Vanderheyden N, Zwaenepoel K, and Croes R
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- Humans, Belgium, Immunohistochemistry, Laboratories, Research Design
- Abstract
Analytical verification and validation of immunohistochemical (IHC) tests and their equipment are common practices for today's anatomic pathology laboratories. Few references or guidelines are available on how this should be performed. The study of Sciensano (the Belgian national competent authority regarding licensing of medical laboratories) performed in 2016, demonstrated a significant interlaboratory variation in validation procedures of IHC tests among Belgian laboratories. These results suggest the unavailability of practical information on the approach to the verification and validation of these tests. The existing Belgian Practice Guideline for the implementation of a quality management system in anatomic pathology laboratories has been reviewed to meet this demand and, in addition, to prepare the laboratories for the EU-IVD revised regulations (IVDR). This paper describes Belgian recommendations for the verification and validation of IHC tests before implementation, for ongoing validation, and for revalidation. For each type of test (according to the IVDR classification and the origin) and its intended use (purpose), it addresses how to perform analytical verification/validation by recommending: (1) the number of cases in the validation set, (2) the performance characteristics to be evaluated, (3) the objective acceptance criteria, (4) the evaluation method for the obtained results, and (5) how and when to revalidate. A literature study and a risk analysis taking into account the majority of variables regarding verification/validation of methods have been performed, resulting in an expert consensus recommendation that is a compromise among achievability, affordability, and patient safety. This new consensus recommendation has been incorporated in the aforementioned ISO 15189:2012-based Practice Guideline., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2024
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27. PD-1, PD-L1, IDO, CD70 and microsatellite instability as potential targets to prevent immune evasion in sarcomas.
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Siozopoulou V, Smits E, Zwaenepoel K, Liu J, Pouliakis A, Pauwels PA, and Marcq E
- Subjects
- Humans, Programmed Cell Death 1 Receptor, Immune Evasion, B7-H1 Antigen genetics, Microsatellite Instability, CD27 Ligand, Sarcoma genetics, Sarcoma therapy, Osteosarcoma, Soft Tissue Neoplasms, Bone Neoplasms
- Abstract
Background: Soft tissue and bone sarcomas are rare entities, hence, standardized therapeutic strategies are difficult to assess. Materials & methods: Immunohistochemistry was performed on 68 sarcoma samples to assess the expression of PD-1, PD-L1, IDO and CD70 in different tumor compartments and molecular analysis was performed to assess microsatellite instability status. Results: PD-1/PD-L1, IDO and CD70 pathways are at play in the immune evasion of sarcomas in general. Soft tissue sarcomas more often show an inflamed phenotype compared with bone sarcomas. Specific histologic sarcoma types show high expression levels of different markers. Finally, this is the first presentation of a microsatellite instability-high Kaposi sarcoma. Discussion/conclusion: Immune evasion occurs in sarcomas. Specific histologic types might benefit from immunotherapy, for which further investigation is needed.
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- 2023
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28. The immune microenvironment characterisation and dynamics in hormone receptor-positive breast cancer before and after neoadjuvant endocrine therapy.
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Oner G, Broeckx G, Van Berckelaer C, Zwaenepoel K, Altintas S, Canturk Z, Tjalma W, Berneman Z, Peeters M, Pauwels P, and van Dam PA
- Subjects
- Humans, Middle Aged, Female, Neoadjuvant Therapy methods, Aromatase Inhibitors therapeutic use, Ki-67 Antigen, Phosphatidylinositol 3-Kinases, Lymphocytes, Tumor-Infiltrating, Tumor Microenvironment, Prognosis, Biomarkers, Tumor, Breast Neoplasms pathology, Triple Negative Breast Neoplasms pathology
- Abstract
Background: Oestrogen receptor positive (ER+)/HER-2 negative breast cancer (BC) is considered to be an immunologically cold tumour compared to triple negative breast cancer. Therefore, the tumour microenvironment (TME) of ER+/HER-2 negative BC is understudied. The aim of this project is to investigate the TME and the immune response during neoadjuvant endocrine therapy (NET) and to correlate this with the treatment response in a real life setting., Methods: Expression of immune checkpoint receptors and immune cells was examined immunohistochemically, pre- and post-NET in a cohort of 56 ER+/HER-2 negative BC patients. They were treated with tamoxifen (n = 16), an aromatase inhibitor (n = 40) or a combination of an aromatase inhibitor with a PI3K inhibitor (n = 11) for a median duration of 6 months (range 1-32 months). Immunohistochemical staining with monoclonal antibodies for PDL-1, PD-1, TIM-3, LAG-3, CTLA-4, CD4, CD68 and FOXP3 were performed. All staining procedures were done according to validated protocols, and scoring was done by a pathologist specialized in breast cancer. Positivity was defined as staining >1% on TILs. Response to NET was evaluated according to tumour size change on imaging and Ki-67 change., Results: The median age was 61.02 (37-90) years. Diameter of tumour size decreased with a mean of 8.1 mm (-16 mm to 45 mm) (p < 0.001) during NET and the value of Ki-67 value decreased with a median of 9 after NET (p < 0.001). An increase in PD-L1 expression after NET showed a trend towards significant (p = 0.088) and CD-4+ T cells significantly increased after NET (p = 0.03). A good response to NET defined as a decrease in tumour size and/or decrease of Ki-67 was found to be associated with a longer duration of NET, a change of CD4+ T-cells and a higher number of CD68+ tumour-associated macrophages before the start of NET., Conclusion: The immune microenvironment plays an important role in ER+/HER-2 negative BC. NET influences the composition and functional state of the infiltrating immune cells. Furthermore, changes in the immune microenvironment are also associated with treatment response., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2023
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29. UAS™-A Urine Preservative for Oncology Applications.
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Jordaens S, Arora A, MacDonald KW, Wood C, Hendrickx JO, Zwaenepoel K, Deben C, Tjalma W, Pauwels P, Beyers K, and Vankerckhoven V
- Abstract
Liquid biopsy is a revolutionary tool that is gaining momentum in the field of cancer research. As a body fluid, urine can be used in non-invasive diagnostics for various types of cancer. We investigated the performance of UAS™ as a preservative for urinary analytes. Firstly, the need for urine preservation was investigated using urine samples from healthy volunteers. Secondly, the performance of UAS™ was assessed for cell-free DNA (cfDNA) and host cell integrity during storage at room temperature (RT) and after freeze-thaw cycling. Finally, UAS™ was used in a clinical setting on samples from breast and prostate cancer patients. In the absence of a preservative, urinary cfDNA was degraded, and bacterial overgrowth occurred at RT. In urine samples stored in UAS™, no microbial growth was seen, and cfDNA and cellular integrity were maintained for up to 14 days at RT. After freeze-thaw cycling, the preservation of host cell integrity and cfDNA showed significant improvements when using UAS™ compared to unpreserved urine samples. Additionally, UAS™ was found to be compatible with several commercially available isolation methods.
- Published
- 2023
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30. Urine biomarkers in cancer detection: A systematic review of preanalytical parameters and applied methods.
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Jordaens S, Zwaenepoel K, Tjalma W, Deben C, Beyers K, Vankerckhoven V, Pauwels P, and Vorsters A
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- Humans, Biomarkers, Liquid Biopsy, Specimen Handling, Neoplasms
- Abstract
The aim of this review was to explore the status of urine sampling as a liquid biopsy for noninvasive cancer research by reviewing used preanalytical parameters and protocols. We searched two main health sciences databases, PubMed and Web of Science. From all eligible publications (2010-2022), information was extracted regarding: (a) study population characteristics, (b) cancer type, (c) urine preanalytics, (d) analyte class, (e) isolation method, (f) detection method, (g) comparator used, (h) biomarker type, (i) conclusion and (j) sensitivity and specificity. The search query identified 7835 records, of which 924 unique publications remained after screening the title, abstract and full text. Our analysis demonstrated that many publications did not report information about the preanalytical parameters of their urine samples, even though several other studies have shown the importance of standardization of sample handling. Interestingly, it was noted that urine is used for many cancer types and not just cancers originating from the urogenital tract. Many different types of relevant analytes have been shown to be found in urine. Additionally, future considerations and recommendations are discussed: (a) the heterogeneous nature of urine, (b) the need for standardized practice protocols and (c) the road toward the clinic. Urine is an emerging liquid biopsy with broad applicability in different analytes and several cancer types. However, standard practice protocols for sample handling and processing would help to elaborate the clinical utility of urine in cancer research, detection and disease monitoring., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
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- 2023
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31. NPY Methylated ctDNA is a Promising Biomarker for Treatment Response Monitoring in Metastatic Colorectal Cancer.
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Janssens K, Vanhoutte G, Lybaert W, Demey W, Decaestecker J, Hendrickx K, Rezaei Kalantari H, Zwaenepoel K, Pauwels P, Fransen E, Op de Beeck K, Van Camp G, Rolfo C, and Peeters M
- Subjects
- Humans, Panitumumab, Bevacizumab, Biomarkers, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Fluorouracil, Leucovorin, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Colonic Neoplasms etiology, Rectal Neoplasms etiology
- Abstract
Purpose: Analysis of methylation markers in liquid biopsies is a promising technique for the follow-up of patients with metastatic colorectal cancer (mCRC), because they can be used in all patients, regardless of their mutational status. Therefore, we studied the value of NPY methylation analysis in circulating tumor DNA (ctDNA) for accurate response monitoring in patients with mCRC in the PANIB trial., Experimental Design: The PANIB trial was a randomized phase II trial designed to compare FOLFOX plus panitumumab and FOLFOX plus bevacizumab in patients with RAS wild-type unresectable mCRC. The results of sequential liquid biopsies were correlated with results of imaging., Results: Forty patients were included from six Belgian hospitals. Analysis of the liquid biopsies revealed that higher baseline levels of methylated ctDNA was associated with a significantly shorter overall survival [HR, 1.015; 95% confidence interval (CI), 1.005-1.025; P = 0.002]. Furthermore, 37 patients provided at least two liquid biopsies. Thirty-one of them showed a decrease in the methylation ratio after the start of therapy, which corresponded with stable disease or response on imaging at the first evaluation. When comparing the panitumumab and bevacizumab arm, significantly higher objective response and early tumor shrinkage rates were observed in the panitumumab arm (P = 0.048 and 0.015, respectively). However, due to a small study population, the trial was underpowered to detect a significant difference in survival., Conclusions: The results of this study confirm that baseline methylated ctDNA is a prognostic marker and indicate that NPY methylation is a promising marker for response monitoring in patients with mCRC., (©2023 American Association for Cancer Research.)
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- 2023
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32. Metal Ion and Guest-Mediated Spontaneous Resolution and Solvent-Induced Chiral Symmetry Breaking in Guanine-Based Metallosupramolecular Networks.
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Cucinotta A, Kahlfuss C, Minoia A, Eyley S, Zwaenepoel K, Velpula G, Thielemans W, Lazzaroni R, Bulach V, Hosseini MW, Mali KS, and De Feyter S
- Subjects
- Stereoisomerism, Catalysis, Metals
- Abstract
Two-dimensional (2D) chirality has been actively studied in view of numerous applications of chiral surfaces such as in chiral resolutions and enantioselective catalysis. Here, we report on the expression and amplification of chirality in hybrid 2D metallosupramolecular networks formed by a nucleobase derivative. Self-assembly of a guanine derivative appended with a pyridyl node was studied at the solution-graphite interface in the presence and absence of coordinating metal ions. In the absence of coordinating metal ions, a monolayer that is representative of a racemic compound was obtained. This system underwent spontaneous resolution upon addition of a coordinating ion and led to the formation of a racemic conglomerate. The spontaneous resolution could also be achieved upon addition of a suitable guest molecule. The mirror symmetry observed in the formation of the metallosupramolecular networks could be broken via the use of an enantiopure solvent, which led to the formation of a globally homochiral surface.
- Published
- 2023
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33. Molecular pathology testing for non-small cell lung cancer: an observational study of elements currently present in request forms and result reports and the opinion of different stakeholders.
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Dufraing K, Van Casteren K, Breyne J, D'Haene N, Van Campenhout C, Vander Borght S, Zwaenepoel K, Rouleau E, Schuuring E, von der Thüsen J, and Dequeker E
- Subjects
- Humans, Liquid Biopsy, Molecular Diagnostic Techniques, Pathology, Molecular, Carcinoma, Non-Small-Cell Lung diagnosis, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms diagnosis, Lung Neoplasms genetics
- Abstract
Background: For patients with non-small cell lung cancer (NSCLC), targeted therapies are becoming part of the standard treatment. It is of question which information the clinicians provide on test requests and how the laboratories adapt test conclusions to this knowledge and regulations., Methods: This study consisted of two components; 1) checking the presence of pre-defined elements (administrative and key for therapy-choice) on completed requests and corresponding reports in Belgian laboratories, both for tissue- and liquid biopsy (LB)-testing and b) opinion analysis from Belgian pathologists/molecular biologists and clinicians during national pathology/oncology meetings., Results: Data from 4 out of 6 Belgian laboratories with ISO-accreditation for LB-testing were analyzed, of which 75% were university hospitals. On the scored requests (N = 4), 12 out of 19 ISO-required elements were present for tissue and 11 for LB-testing. Especially relevant patient history, such as line of therapy (for LB), tumor histology and the reason for testing were lacking. Similarly, 11 and 9 out of 18 elements were present in the reports (N = 4) for tissue and LB, respectively. Elements that pathologists/molecular biologists (N = 18) were missing on the request were the initial activating mutation, previous therapies, a clinical question and testing-related information. For reporting, an item considered important by both groups is the clinical interpretation of the test result. In addition, clinicians (N = 28) indicated that they also wish to read the percentage of neoplastic cells., Conclusions: Communication flows between the laboratory and the clinician, together with possible pitfalls were identified. Based on the study results, templates for complete requesting and reporting were proposed., (© 2022. The Author(s).)
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- 2022
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34. NTRK Gene Fusion Detection in a Pan-Cancer Setting Using the Idylla GeneFusion Assay.
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Sorber L, Van Dorst B, Bellon E, Zwaenepoel K, Lambin S, De Winne K, Lardon F, Pauwels P, and Siozopoulou V
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- Biomarkers, Tumor genetics, Gene Fusion, Humans, Oncogene Proteins, Fusion genetics, RNA, Receptor, trkA analysis, Receptor, trkA genetics, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Neoplasms diagnosis, Neoplasms genetics, Neoplasms metabolism
- Abstract
Recently, approval of tyrosine receptor kinase (TRK) inhibitors by Food and Drug Administration and European Medicines Agency in NTRK fusion-positive cancer types has led to a variety of proposed testing algorithms. In this study, performance of the fully automated Idylla GeneFusion Assay was assessed in a set of clinically relevant cancer types, including glioblastoma, non-small-cell lung cancer, microsatellite instability-positive colorectal cancer, and thyroid carcinoma. Analysis with the Idylla GeneFusion Assay revealed significant differences in baseline RNA expression profile between the different cancer types, which corresponded to both literature and pan-TRK immunohistochemical staining. Compared with the RNA-based Oncomine Focus Assay, the Idylla GeneFusion Assay demonstrated an overall percentage agreement, positive percentage agreement, and negative percentage agreement of 92.7%, 81.8%, and 93.8%, respectively; and the pan-TRK immunohistochemistry demonstrated an overall percentage agreement, positive percentage agreement, and negative percentage agreement of 82.1%, 45.5%, and 85.7%, respectively. These findings highlighted the importance of tailoring NTRK testing algorithms per cancer type. In a small subset, data from the RNA-based Archer FusionPlex Assay were also available. NTRK fusion detection efficiency was compared between the four NTRK testing modalities, with a high concordance between the PCR-based methods. Last, RNA degradation was observed when using the Idylla GeneFusion Assay on snap frozen tissue samples as these are nonfixated. This might be countered by increasing the amount of sample input. To conclude, the Idylla GeneFusion Assay has shown a clear potential in identifying NTRK fusions., (Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
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- 2022
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35. Are anaplastic lymphoma kinase (ALK) and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation driver biomarkers of pulmonary neuroendocrine tumors (NETs) and carcinomas (NECs)?
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Hiddinga B, Zwaenepoel K, Janssens A, Van Meerbeeck J, and Pauwels P
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- Anaplastic Lymphoma Kinase genetics, Anaplastic Lymphoma Kinase metabolism, Biomarkers metabolism, DNA metabolism, DNA Methylation, DNA Modification Methylases genetics, DNA Modification Methylases metabolism, DNA Repair Enzymes, Guanine analogs & derivatives, Humans, O(6)-Methylguanine-DNA Methyltransferase metabolism, Retrospective Studies, Temozolomide therapeutic use, Tumor Suppressor Proteins genetics, Tumor Suppressor Proteins metabolism, Carcinoid Tumor genetics, Carcinoma, Neuroendocrine genetics, Lung Neoplasms genetics, Neuroendocrine Tumors genetics, Neuroendocrine Tumors pathology
- Abstract
Background: Novel targets in neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) are needed to improve outcome. The presence of O6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation in NETs and NECs may act as a predictive marker for response on treatment with temozolomide. As anaplastic lymphoma kinase (ALK) plays an important role in the nervous system we hypothesized that ALK rearrangement can act as a biomarker in patients with NETs and NECs., Materials and Methods: We performed a retrospective analysis to establish the frequency of MGMT promoter methylation and ALK expression in tissue samples of patients with NETs and NECs., Results: 21% (14/67) of patients tested positive for MGMT promoter methylation. MGMT promoter methylation was present in 33% (3/9) patients with typical carcinoid, in 22% (2/9) patients with atypical carcinoid, in 22% (8/37) patients with small cell lung cancer and in 8% (1/12) patient with large cell neuroendocrine carcinoma. ALK- expression was present in 14% (10 of 70 patients). In all of these patients, no ALK-rearrangement nor ALK-mutation was revealed., Conclusions: Routine testing of NET and NEC samples for an ALK rearrangement is not recommended as ALK-expression is not associated with an ALK-rearrangement. Routine testing of NET and NEC samples for MGMT will detect a promoter hypermethylation in a sizable minority of patients who are eligible for a targeted treatment with temozolomide., Competing Interests: CONFLICTS OF INTEREST Authors have no conflicts of interest to declare., (Copyright: © 2022 Hiddinga et al.)
- Published
- 2022
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36. Cusatuzumab for treatment of CD70-positive relapsed or refractory cutaneous T-cell lymphoma.
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Leupin N, Zinzani PL, Morschhauser F, Dalle S, Maerevoet M, Michot JM, Ribrag V, Offner F, Beylot-Barry M, Moins-Teisserenc H, Zwaenepoel K, de Winne K, Battistella M, Hultberg A, Gandini D, Moshir M, Jacobs J, Delahaye T, Khan A, Zabrocki P, Silence K, van Rompaey L, Borg C, Motta G, Melle F, Calleri A, Pauwels P, de Haard H, Pileri S, and Bagot M
- Subjects
- CD27 Ligand, Humans, Neoplasm Recurrence, Local pathology, Treatment Outcome, Antibodies, Monoclonal adverse effects, Antineoplastic Agents therapeutic use, Lymphoma, T-Cell, Cutaneous drug therapy, Skin Neoplasms drug therapy
- Abstract
Background: The clinical benefit of cusatuzumab, a CD70-directed monoclonal antibody with enhanced effector functions, was investigated in patients with relapsed/refractory (R/R) cutaneous T-cell lymphoma (CTCL)., Methods: In this cohort expansion of the ARGX-110-1201 study, 27 patients with R/R CTCL received cusatuzumab at 1 (n = 11) or 5 mg/kg (n = 16) once every 3 weeks to investigate its safety, dose, and exploratory efficacy. The pharmacokinetics, immunogenicity, CD70 expression, and CD70/CD27 biology were also assessed., Results: The most common adverse events included infusion-related reactions, pyrexia, and asthenia. Eighteen serious adverse events (grade 1-3) were reported in 11 patients; 1 of these (vasculitis) was considered drug-related. For 8 of the 11 patients receiving 1 mg/kg, anti-drug antibodies (ADAs) affected the minimal concentration, and this resulted in undetectable cusatuzumab concentrations at the end of treatment and, in some cases, a loss of response. This effect was greatly reduced in the patients receiving 5 mg/kg. The overall response rate was 23%; this included 1 complete response and 5 partial responses (PRs) in 26 of the 27 evaluable patients. In addition, 9 patients achieved stable disease. The mean duration on cusatuzumab was 5.2 months, and the median duration was 2.5 months. Patients with Sézary syndrome (SS) achieved a 60% PR rate with a dosage of 5 mg/kg and a 33% PR rate with a dosage of 1 mg/kg; this resulted in an overall response rate of 50% for patients with SS at both doses., Conclusions: Cusatuzumab was well tolerated, and antitumor activity was observed at both 1 and 5 mg/kg in highly pretreated patients with R/R CTCL. The observed dose-dependent effect on exposure supports the use of 5 mg/kg for future development., (© 2021 American Cancer Society.)
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- 2022
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37. Evaluation of Cytologic Sample Preparations for Compatibility With Nucleic Acid Analysis.
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Sorber L, Claes B, Zwaenepoel K, Van Dorst B, De Winne K, Fransen E, Wener R, Lapperre T, Lardon F, and Pauwels P
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- Humans, Paraffin Embedding methods, RNA genetics, Specimen Handling methods, Tissue Fixation methods, Formaldehyde, Nucleic Acids
- Abstract
Objectives: In this study, the influence of several key elements of the cytologic sample workflow on DNA and RNA content was evaluated., Methods: The A549 cell line, patient-derived organoids, and pleural effusions were used to investigate the effect of (1) several collection media and delayed time to processing; (2) cytology specimens; (3) cytologic staining; and (4) formalin-fixed, paraffin-embedded (FFPE) cell block processing on nucleic acid quality and quantity as determined by fragment analyzer, Qubit analysis (Thermo Fisher Scientific), and quantitative polymerase chain reaction-based analysis on the Idylla platform (Biocartis)., Results: Alcohol-based collection media (CytoRich Red [Thermo Fisher Scientific] and EtOH95%) displayed high DNA and RNA preservation capacity, while phosphate-buffered saline and, to a lesser extent, formalin were associated with high RNA quality. Cytospin and smear cytology specimens were subject to DNA and RNA loss. Cytologic staining had no further impact on sample quality, hence destaining is not necessary. Both H&E-stained and unstained FFPE sections are compatible with nucleic acid analysis, despite a strong decrease in DNA and RNA quality., Conclusions: Although several key elements of the cytologic sample workflow have an influence on DNA and RNA quality and quantity, the selection of these elements is also dependent on the downstream (ancillary) testing methods., (© American Society for Clinical Pathology, 2021.)
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- 2022
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38. Excellent Response to MEK Inhibition in an AGK-BRAF Gene Fusion Driven Carcinoma: Case Report and Literature Review.
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Domen A, Paesschen CV, Zwaenepoel K, Lambin S, Pauwels P, Rasschaert M, Segelov E, Peeters M, and Prenen H
- Subjects
- Carcinoma drug therapy, Carcinoma genetics, Carcinoma pathology, Enzyme Inhibitors therapeutic use, Female, Humans, Middle Aged, Mitogen-Activated Protein Kinase Kinases antagonists & inhibitors, Mutation, Myoepithelioma genetics, Myoepithelioma pathology, Oncogene Proteins, Fusion genetics, Protein Kinase Inhibitors therapeutic use, Soft Tissue Neoplasms genetics, Soft Tissue Neoplasms pathology, Mitogen-Activated Protein Kinase Kinases genetics, Myoepithelioma drug therapy, Phosphotransferases (Alcohol Group Acceptor) genetics, Proto-Oncogene Proteins B-raf genetics, Soft Tissue Neoplasms drug therapy
- Abstract
Background: Soft tissue myoepithelial carcinomas (STMC) are a rare, malignant subgroup of myoepithelial tumors that arise typically in glandular or ductal tissues, but also in the bone and soft and cutaneous tissues. Due to its rarity, there is no consensus regarding the treatment of STMC, including chemotherapy or other systemic agents for metastatic STMC., Case Report: A chemotherapy- and regorafenib-refractory STMC, harboring an AGK-BRAF fusion, was successfully treated using MEK-inhibition with cobimetinib in monotherapy. MEK-inhibition with cobimetinib effectively silenced paradoxical MAP kinase/ERK-signaling pathway activation after regorafenib monotherapy, and resulted in a significant and durable clinical response., Conclusion: This effect of MEK-inhibition in STMC harboring an AGK-BRAF fusion has not been previously reported and contributes to the existing, yet limited, knowledge on the treatment of BRAF fusion-driven tumors. Also, our case highlights the importance of next generation sequencing in driving further rational therapeutic choices to provide disease control and palliation., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
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- 2022
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39. Immuno-PET Molecular Imaging of RANKL in Cancer.
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Dewulf J, Vangestel C, Verhoeven Y, De Waele J, Zwaenepoel K, van Dam PA, Elvas F, and Van den Wyngaert T
- Abstract
Purpose: The involvement of RANK/RANKL signaling in the tumor microenvironment (TME) in driving response or resistance to immunotherapy has only very recently been recognized. Current quantification methods of RANKL expression suffer from issues such as sensitivity, variability, and uncertainty on the spatial heterogeneity within the TME, resulting in conflicting reports on its reliability and limited use in clinical practice. Non-invasive molecular imaging using immuno-PET is a promising approach combining superior targeting specificity of monoclonal antibodies (mAb) and spatial, temporal and functional information of PET. Here, we evaluated radiolabeled anti-RANKL mAbs as a non-invasive biomarker of RANKL expression in the TME., Experimental Design: Anti-human RANKL mAbs (AMG161 and AMG162) were radiolabeled with
89 Zr using the bifunctional chelator DFO in high yield, purity and with intact binding affinity. After assessing the biodistribution in healthy CD-1 nude mice, [89 Zr]Zr-DFO-AMG162 was selected for further evaluation in ME-180 (RANKL-transduced), UM-SCC-22B (RANKL-positive) and HCT-116 (RANKL-negative) human cancer xenografts to assess the feasibility of in vivo immuno-PET imaging of RANKL., Results: [89 Zr]Zr-DFO-AMG162 was selected as the most promising tracer for further validation based on biodistribution experiments. We demonstrated specific accumulation of [89 Zr]Zr-DFO-AMG162 in RANKL transduced ME-180 xenografts. In UM-SCC-22B xenograft models expressing physiological RANKL levels, [89 Zr]Zr-DFO-AMG162 imaging detected significantly higher signal compared to control [89 Zr]Zr-DFO-IgG2 and to RANKL negative HCT-116 xenografts. There was good visual agreement with tumor autoradiography and immunohistochemistry on adjacent slides, confirming these findings., Conclusions: [89 Zr]Zr-DFO-AMG162 can detect heterogeneous RANKL expression in the TME of human cancer xenografts, supporting further translation of RANKL immuno-PET to evaluate tumor RANKL distribution in patients.- Published
- 2021
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40. Prognostic and Predictive Biomarkers in Non-Small Cell Lung Cancer Patients on Immunotherapy-The Role of Liquid Biopsy in Unraveling the Puzzle.
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Augustus E, Zwaenepoel K, Siozopoulou V, Raskin J, Jordaens S, Baggerman G, Sorber L, Roeyen G, Peeters M, and Pauwels P
- Abstract
In the last decade, immunotherapy has been one of the most important advances in the non-small cell lung cancer (NSCLC) treatment landscape. Nevertheless, only a subset of NSCLC patients benefits from it. Currently, the only Food and Drug Administration (FDA) approved diagnostic test for first-line immunotherapy in metastatic NSCLC patients uses tissue biopsies to determine the programmed death ligand 1 (PD-L1) status. However, obtaining tumor tissue is not always feasible and puts the patient at risk. Liquid biopsy, which refers to the tumor-derived material present in body fluids, offers an alternative approach. This less invasive technique gives real-time information on the tumor characteristics. This review addresses different promising liquid biopsy based biomarkers in NSCLC patients that enable the selection of patients who benefit from immunotherapy and the monitoring of patients during this therapy. The challenges and the opportunities of blood-based biomarkers such as cell-free DNA (cfDNA), circulating tumor cells (CTCs), exosomes, epigenetic signatures, microRNAs (miRNAs) and the T cell repertoire will be addressed. This review also focuses on the less-studied feces-based and breath-based biomarkers.
- Published
- 2021
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41. Immunohistochemistry as a screening tool for NTRK gene fusions: results of a first Belgian ring trial.
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De Winne K, Sorber L, Lambin S, Siozopoulou V, Beniuga G, Dedeurwaerdere F, D'Haene N, Habran L, Libbrecht L, Van Huysse J, Weynand B, Wouters K, Pauwels P, and Zwaenepoel K
- Subjects
- Belgium, Genetic Predisposition to Disease, Humans, Laboratory Proficiency Testing, Neoplasms pathology, Observer Variation, Phenotype, Predictive Value of Tests, Reproducibility of Results, Biomarkers, Tumor genetics, Early Detection of Cancer, Gene Fusion, Immunohistochemistry, Neoplasms genetics, Receptors, Nerve Growth Factor genetics
- Abstract
A Belgian ring trial for pan-TRK immunohistochemistry (IHC) staining was organised to harmonise pan-TRK IHC staining protocols and interpretation. As a reference method, the VENTANA pan-TRK Assay (clone EPR17341) on the Benchmark Ultra platform was selected. Six samples were selected: 2 negative, 2 fusion positive and 2 samples with wild-type endogenous TRK expression. Each participating laboratory stained the slides using their routine pan-TRK IHC and reported their results. In addition, they were asked to return one TRK-stained slide from each case. The coordinating lab evaluated these slides, compared them with the reference method and scored them. Two clones were used during the ring trial: A7H6R (Cell Signaling) and EPR17341 (Abcam/Ventana). Seven protocols achieved a sufficient performance mark, and three labs were advised to further optimise the protocol. Interpretation of pan-TRK IHC proved to be challenging in cases with physiological TRK expression. In addition, depending on the NTRK fusion partner, the staining can vary strongly in both intensity and staining pattern. Labs using the Ventana ready-to-use system based on the EPR17341 clone and using the recommended protocol settings scored best. However, given some small optimisation, all labs scored well on the technical staining and the succeeding evaluation.
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- 2021
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42. Immune Checkpoint Inhibitory Therapy in Sarcomas: Is There Light at the End of the Tunnel?
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Siozopoulou V, Domen A, Zwaenepoel K, Van Beeck A, Smits E, Pauwels P, and Marcq E
- Abstract
Soft tissue and bone sarcomas are a very heterogeneous group of tumors with many subtypes for which diagnosis and treatment remains a very challenging task. On top of that, the treatment choices are limited, and the prognosis of aggressive sarcomas remains poor. Immune checkpoint inhibitors (ICIs) have drawn a lot of attention last years because of their promising response rates and their durable effects. ICIs are currently widely used in the daily routine practice for the treatment of a different malignancies, such as melanoma, Hodgkin lymphoma, and non-small cell lung carcinoma. Still, ICIs are not included in the standard treatment protocols of the different sarcoma types. However, a plethora of clinical trials investigates the clinical benefit of ICIs in sarcomas. There is clear need to develop predictive biomarkers to determine which sarcoma patients are most likely to benefit from immune checkpoint blockade. This review will focus on (i) the clinical trial results on the use of ICIs in different sarcoma types; and on (ii) possible biomarkers predictive for the effectiveness of these drugs in sarcomas.
- Published
- 2021
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43. Staining Performance of ALK and ROS1 Immunohistochemistry and Influence on Interpretation in Non-Small-Cell Lung Cancer.
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Keppens C, von der Thüsen J, Pauwels P, Ryska A, 't Hart N, Schuuring E, Miller K, Thunnissen E, Zwaenepoel K, and Dequeker EMC
- Subjects
- Humans, In Situ Hybridization, Fluorescence methods, Laboratories, Hospital, Pathologists, Proto-Oncogene Mas, Sensitivity and Specificity, Anaplastic Lymphoma Kinase metabolism, Carcinoma, Non-Small-Cell Lung metabolism, Immunohistochemistry methods, Lung Neoplasms metabolism, Protein-Tyrosine Kinases metabolism, Proto-Oncogene Proteins metabolism
- Abstract
Selection of non-small-cell lung cancer patients for treatment relies on the detection of expression of anaplastic lymphoma kinase (ALK) and ROS proto-oncogene 1 (ROS1) protein by immunohistochemistry (IHC). We evaluated staining performance for different IHC protocols and laboratory characteristics, and their influence on ALK and ROS1 interpretation during external quality assessment schemes between 2015 and 2018. Participants received five formalin-fixed, paraffin-embedded cases for staining by their routine protocol, whereafter at least two pathologists scored them simultaneously under a multihead microscope and awarded a graded expert staining score (ESS) from 1 to 5 points based on staining quality. European Conformity in Vitro Diagnostic kits (such as D5F3) revealed a better ALK ESS compared with laboratory-developed tests. ESS was indifferent to the applied antibody dilution or a recent protocol change. Lower ESSs were observed for higher antibody incubation times and temperatures. ESS for various ROS1 protocols were largely similar. Overall, for both markers, ESS improved over time and for repeated external quality assessment participation but was independent of laboratory setting or experience. Except for ROS1, ESS positively correlated with laboratory accreditation. IHC stains with lower ESS correlated with increased error rates in ALK and ROS1 interpretation and analysis failures. Laboratory characteristics differently affected staining quality and interpretation, and laboratories should assess both aspects, and less common protocols need improvement in staining performance., (Copyright © 2020 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
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- 2020
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44. Sensitive detection methods are key to identify secondary EGFR c.2369C>T p.(Thr790Met) in non-small cell lung cancer tissue samples.
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Keppens C, Dequeker EMC, Rouleau E, 't Hart N, Bubendorf L, Dufraing K, Garrec C, Guéguen P, Lamy A, Marchetti A, Pauwels P, Ryska A, Tack V, Tornillo L, Van Casteren K, von der Thüsen JH, Zwaenepoel K, Lissenberg-Witte B, Thunnissen E, and Schuuring E
- Subjects
- Carcinoma, Non-Small-Cell Lung diagnosis, Carcinoma, Non-Small-Cell Lung enzymology, ErbB Receptors genetics, Follow-Up Studies, Genetic Testing methods, Genetic Testing standards, Humans, Longitudinal Studies, Lung Neoplasms diagnosis, Lung Neoplasms enzymology, Polymorphism, Single Nucleotide, Quality Control, Tumor Cells, Cultured, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms genetics, Mutation
- Abstract
Background: Correct identification of the EGFR c.2369C>T p.(Thr790Met) variant is key to decide on a targeted therapeutic strategy for patients with acquired EGFR TKI resistance in non-small cell lung cancer. The aim of this study was to evaluate the correct detection of this variant in 12 tumor tissue specimens tested by 324 laboratories participating in External Quality Assessment (EQA) schemes., Methods: Data from EQA schemes were evaluated between 2013 and 2018 from cell lines (6) and resections (6) containing the EGFR c.2369C>T p.(Thr790Met) mutation. Adequate performance was defined as the percentage of tests for which an outcome was available and correct. Additional data on the used test method were collected from the participants. Chi-squared tests on contingency tables and a biserial rank correlation were applied by IBM SPSS Statistics version 25 (IBM, Armonk, NY, USA)., Results: In 26 of the 1190 tests (2.2%) a technical failure occurred. For the remaining 1164 results, 1008 (86.6%) were correct, 151 (12.9%) were false-negative and 5 (0.4%) included incorrect mutations. Correct p.(Thr790Met) detection improved over time and for repeated scheme participations. In-house non-next-generation sequencing (NGS) techniques performed worse (81.1%, n = 293) compared to non-NGS commercial kits (85.2%, n = 656) and NGS (97.0%, n = 239). Over time there was an increase in the users of NGS. Resection specimens performed worse (82.6%, n = 610 tests) compared to cell line material (90.9%, n = 578 tests), except for NGS (96.3%, n = 344 for resections and 98.6%, n = 312 for cell lines). Samples with multiple mutations were more difficult compared to samples with the single p.(Thr790Met) variant. A change of the test method was shown beneficial to reduce errors but introduced additional analysis failures., Conclusions: A significant number of laboratories that offer p.(Thr790Met) testing did not detect this relevant mutation compared to the other EQA participants. However, correct identification of this variant is improving over time and was higher for NGS users. Revising the methodology might be useful to resolve errors, especially for resection specimens with low frequency or multiple variants. EQA providers should include challenging resections in the scheme.
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- 2020
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45. The art of obtaining a high yield of cell-free DNA from urine.
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Augustus E, Van Casteren K, Sorber L, van Dam P, Roeyen G, Peeters M, Vorsters A, Wouters A, Raskin J, Rolfo C, Zwaenepoel K, and Pauwels P
- Subjects
- Adult, Aged, Centrifugation methods, Female, Healthy Volunteers, Humans, Liquid Biopsy, Male, Middle Aged, Neoplasms pathology, Pilot Projects, Temperature, Time Factors, Urine Specimen Collection methods, Young Adult, Cell-Free Nucleic Acids urine, Diagnostic Tests, Routine standards, Neoplasms urine, Urinalysis standards, Urine Specimen Collection standards
- Abstract
Although liquid biopsies offer many advantages over tissue biopsies, they are not yet standard practice. An important reason for the lack of implementation is the unavailability of well standardized techniques and guidelines, especially for pre-analytical conditions which are an important factor causing the current sensitivity issues. To overcome these limitations, we investigated the effect of several pre-analytical conditions on the concentration of cell-free DNA (cfDNA) and cellular genomic DNA (gDNA) contamination. Urine samples from healthy volunteers (HVs) and cancer patients were collected and processed according to specific pre-analytical conditions. Our results show that in samples with a relatively small volume more than 50% of the cfDNA can be found in the first 50 mL of the urine sample. The total DNA concentration increased again when samples were collected more than 3.5 hours apart. Adding preservative to urine samples is recommended to obtain high concentrations of cfDNA. To remove the cellular content, high speed centrifugation protocols as 4,000g 10min or 3,000g 15min are ideal for urine collected in cfDNA Urine Preserve (Streck). Although this study was a pilot study and needs to be confirmed in a larger study population, clear trends in the effect of several pre-analytical conditions were observed., Competing Interests: The authors have declared that no competing interests exist.
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- 2020
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46. Clinical Performance of the Idylla MSI Test for a Rapid Assessment of the DNA Microsatellite Status in Human Colorectal Cancer.
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Zwaenepoel K, Holmgaard Duelund J, De Winne K, Maes V, Weyn C, Lambin S, Dendooven R, Broeckx G, Steiniche T, and Pauwels P
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- Adolescent, Adult, Aged, Aged, 80 and over, Colorectal Neoplasms diagnosis, Female, Humans, Immunohistochemistry, Male, Middle Aged, Necrosis pathology, Neoplasm Staging, Reproducibility of Results, Sensitivity and Specificity, Young Adult, Biomarkers, Tumor, Colorectal Neoplasms genetics, Genetic Testing methods, Genetic Testing standards, Microsatellite Instability, Microsatellite Repeats
- Abstract
In this study, the clinical performance of the Idylla MSI test (investigational use only) was evaluated in 330 colorectal carcinoma samples (all stages). This test is fully automated, from formalin-fixed, paraffin-embedded slide to result, and gives a result in <2.5 hours. Compared with the Promega MSI Analysis System version 1.2, an overall agreement, sensitivity, and specificity of 99.7%, 98.7%, and 100%, respectively, was reached. Whereas seven samples were invalid with the Promega MSI Analysis System, only two were invalid with the Idylla MSI test. Compared with the historical immunohistochemistry (IHC) data, overall agreement, sensitivity, and specificity of 98.7%, 94.4%, and 100%, respectively, were observed. Tumor mutation burden analysis of the discordant IHC cases was in favor of the Idylla MSI test result in three of the four samples. Furthermore, for those cases where the IHC data were invalid or hard to interpret because sole loss of one DNA mismatch repair deficiency marker was observed, Idylla MSI test results were always valid and accurate. Herein, the Idylla MSI test has been shown to be an accurate, fast screening assay for the detection of microsatellite status in colorectal cancer patients, with a low number of invalid results., (Copyright © 2020 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)
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- 2020
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47. Specialized Blood Collection Tubes for Liquid Biopsy: Improving the Pre-analytical Conditions.
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Sorber L, Zwaenepoel K, Jacobs J, De Winne K, Van Casteren K, Augustus E, Lardon F, Prenen H, Peeters M, Van Meerbeeck J, Roeyen G, Rolfo C, and Pauwels P
- Subjects
- Blood Specimen Collection, Cell-Free Nucleic Acids blood, Humans, Biomarkers, Tumor, Liquid Biopsy methods, Neoplasms blood, Neoplasms diagnosis
- Abstract
Introduction: The potential of circulating cell-free DNA (cfDNA) analysis as a liquid biopsy has led to the development of several specialized measuring tools. Interest in the (pre-)analytical conditions of the liquid biopsy workflow has increased over the past few years., Methods: In this study, we performed a systematic review of the cfDNA stabilizing efficacy in standard EDTA and specialized blood collection tubes (BCTs), namely CellSave, Norgen, PAXgene, Roche, and Streck tubes, and compared the efficacy of the latter three BCTs in a situation resembling the clinical setting. Blood samples were collected from ten KRAS-mutated metastatic cancer patients and stored for 72 h. During this time, samples were shaken and kept at either 6 °C or at room temperature for 24 h to mimic transport., Results: We demonstrated that while cfDNA levels in EDTA tubes are only stable for a couple of (≤ 6) hours, they could be sustained for at least 48-72 h in all three specialized BCTs, irrespective of temperature. This timespan enables a fast turnaround time, which is one of the advantages of liquid biopsy., Conclusions: The choice between these specialized BCTs is less vital when they are processed correctly within a few days.
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- 2020
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48. The immunologic aspects in hormone receptor positive breast cancer.
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Oner G, Altintas S, Canturk Z, Tjalma W, Van Berckelaer C, Broeckx G, Zwaenepoel K, Tholhuijsen M, Verhoeven Y, Berneman Z, Peeters M, Pauwels P, and van Dam PA
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- Female, Humans, Tumor Microenvironment, Breast Neoplasms immunology
- Abstract
Background: Although hormone receptor positive/HER2-negative (HR +/HER2-) breast cancer is the most diagnosed breast cancer type, the immunologic aspects HR positive breast cancer (BC) has been neglected until recently. The purpose of this paper is to review the current knowledge of the immune environment in HR positive BC and the potential use of immunotherapy in these patients., Method: A computer-based literature research was carried out using PubMed, American Society of Clinical Oncology Annual Meeting (ASCO) and San Antonio Breast Cancer Symposium (SABCS)., Results: The tumour microenvironment (TME), with infiltrating immune cells, plays an important role in HR positive BC. However, the effects of these immune cells are different in the luminal cancers compared to the other breast cancer types. Even though PD-1 and PD-L1 are less expressed in HR positive BC, pathological complete response (pCR) was more often seen after PD-1 inhibitor treatment in patients with an increased expression. The studies support the assertion that endocrine therapy has immunomodulatory effect., Conclusion: The reviewed literature indicates that immune cells play an important role in HR positive BC. Considerably more research is needed to determine the real effect of the TME in this patient group., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2020
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49. The Role of c-Met as a Biomarker and Player in Innate and Acquired Resistance in Non-Small-Cell Lung Cancer: Two New Mutations Warrant Further Studies.
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Van Der Steen N, Zwaenepoel K, Mazzaschi G, A Luirink R, P Geerke D, Op de Beeck K, Hermans C, Tiseo M, Van Schil P, Lardon F, Germonpré P, Rolfo C, Giovannetti E, J Peters G, and Pauwels P
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- Adult, Aged, ErbB Receptors genetics, Female, Gene Amplification, Gene Expression Regulation, Neoplastic, Humans, Male, Middle Aged, Neoplasm Metastasis, Tumor Suppressor Protein p53 genetics, Biomarkers, Tumor metabolism, Carcinoma, Non-Small-Cell Lung genetics, Drug Resistance, Neoplasm genetics, Lung Neoplasms genetics, Mutation genetics, Proto-Oncogene Proteins c-met genetics
- Abstract
The c-Met receptor is a therapeutically actionable target in non-small-cell lung cancer (NSCLC), with one approved drug and several agents in development. Most suitable biomarkers for patient selection include c-Met amplification and exon-14 skipping. Our retrospective study focused on the frequency of different c-Met aberrations (overexpression, amplification and mutations) in 153 primary, therapy-naïve resection samples and their paired metastases, from Biobank@UZA. Furthermore, we determined the correlation of c-Met expression with clinicopathological factors, Epidermal Growth Factor Receptor (EGFR)-status and TP53 mutations. Our results showed that c-Met expression levels in primary tumors were comparable to their respective metastases. Five different mutations were detected by deep sequencing: three (E168D, S203T, N375S) previously described and two never reported (I333T, G783E). I333T, a new mutation in the Sema(phorin) domain of c-Met, might influence the binding of antibodies targeting the HGF-binding domain, potentially causing innate resistance. E168D and S203T mutations showed a trend towards a correlation with high c-Met expression ( p = 0.058). We found a significant correlation between c-MET expression, EGFR expression ( p = 0.010) and EGFR mutations ( p = 0.013), as well as a trend ( p = 0.057) with regards to TP53 mutant activity. In conclusion this study demonstrated a strong correlation between EGFR mutations, TP53 and c-Met expression in therapy-naïve primary resection samples. Moreover, we found two new c-Met mutations that warrant further studies.
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- 2019
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50. Screening a Broad Range of Solid and Haematological Tumour Types for CD70 Expression Using a Uniform IHC Methodology as Potential Patient Stratification Method.
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Flieswasser T, Camara-Clayette V, Danu A, Bosq J, Ribrag V, Zabrocki P, Van Rompaey L, de Haard H, Zwaenepoel K, Smits E, Pauwels P, and Jacobs J
- Abstract
The constitutive expression of CD70 has been described in various haematological and solid tumour types. In addition, the co-expression of its receptor in tumours has been demonstrated, mediating tumour cell proliferation. Although CD70 expression is a prerequisite to enrol patients in solid tumour clinical trials using anti-CD70 immunotherapy, there is currently no standardised test to evaluate CD70 expression. These differences in immunohistochemistry (IHC) protocols make it challenging to compare the expression levels that were obtained in different studies, pointing out the need for one uniform methodology. In this retrospective study, over 600 tumour samples from different solid and haematological malignancies were analysed while using one validated IHC method. CD70 and CD27 expression was demonstrated in a broad range of tumour types. In solid tumours, 43% demonstrated CD70 positivity with the highest degree in renal cell carcinoma (79.5%). Kaposi sarcoma showed no CD70 expression on the tumour cells. In lymphoma samples, 58% demonstrated CD70 positivity. Moreover, the co-expression of CD70 and CD27 was observed in 39% of lymphoma samples. These findings highlight the need to further explore anti-CD70 therapies in a broad range of CD70 expressing tumour types and in doing so, implementing one standardised protocol to define CD70 overexpression to use it as a diagnostic tool.
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- 2019
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