250 results on '"Sagaert, X"'
Search Results
52. FOXP1, a gene highly expressed in a subset of diffuse large B-cell lymphoma, is recurrently targeted by genomic aberrations
- Author
-
UCL - MD/MINT - Département de médecine interne, UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique, UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Service d'hématologie, Wlodarska, Iwona, Veyt, E, De Paepe, P, Vandenberghe, Peter, Nooijen, P, Théate, Ivan, Michaux, Lucienne, Sagaert, X, Marynen, Peter, Hagemeijer, Anne, De Wolf- Peeters, C, UCL - MD/MINT - Département de médecine interne, UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique, UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Service d'hématologie, Wlodarska, Iwona, Veyt, E, De Paepe, P, Vandenberghe, Peter, Nooijen, P, Théate, Ivan, Michaux, Lucienne, Sagaert, X, Marynen, Peter, Hagemeijer, Anne, and De Wolf- Peeters, C
- Abstract
The transcription factor Forkhead box protein P1 (FOXP1) is highly expressed in a proportion of diffuse large B-cell lymphoma (DLBCL). In this report, we provide cytogenetic and fluorescence in situ hybridization ( FISH) data showing that FOXP1 (3p13) is recurrently targeted by chromosome translocations. The genomic rearrangement of FOXP1 was identified by FISH in three cases with a t(3;14)(p13;q32) involving the immunoglobulin heavy chain (IGH) locus, and in one case with a variant t(2;3) affecting sequences at 2q36. These aberrations were associated with strong expression of FOXP1 protein in tumor cells, as demonstrated by immunohistochemistry (IHC). The cases with t(3p13) were diagnosed as DLBCL ( x 1), gastric MALT lymphoma ( x 1) and B-cell non-Hodgkin's lymphoma, not otherwise specified ( x 2). Further IHC and FISH studies performed on 98 cases of DLBCL and 93 cases of extranodal marginal zone lymphoma showed a high expression of FOXP1 in approximately 13 and 12% of cases, respectively. None of these cases showed, however, FOXP1 rearrangements by FISH. However, over-representation of the FOXP1 locus found in one additional case of DLBCL may represent another potential mechanism underlying an increased expression of this gene.
- Published
- 2005
53. Subacute cytomegalovirus appendicitis in a renal transplant recipient
- Author
-
Posen, A., primary, Renckens, I., additional, Sagaert, X., additional, and Kuypers, D., additional
- Published
- 2012
- Full Text
- View/download PDF
54. The accuracy of positron emission tomography in the detection of posttransplant lymphoproliferative disorder
- Author
-
Dierickx, D., primary, Tousseyn, T., additional, Requile, A., additional, Verscuren, R., additional, Sagaert, X., additional, Morscio, J., additional, Wlodarska, I., additional, Herreman, A., additional, Kuypers, D., additional, Van Cleemput, J., additional, Nevens, F., additional, Dupont, L., additional, Uyttebroeck, A., additional, Pirenne, J., additional, De Wolf-Peeters, C., additional, Verhoef, G., additional, Brepoels, L., additional, and Gheysens, O., additional
- Published
- 2012
- Full Text
- View/download PDF
55. OC-07: Clinical and Molecular Effects of Treatment with Bevacizumab, Capecitabine and Oxaliplatin in Rectal Cancer
- Author
-
Verstraete, M., primary, Debucquoy, A., additional, Devos, E., additional, Chiritescu, G., additional, Dumon, K., additional, Machiels, J.P., additional, Penninckx, F., additional, Sagaert, X., additional, Van Cutsem, E., additional, and Haustermans, K., additional
- Published
- 2012
- Full Text
- View/download PDF
56. Axe Beam: Encouraging Early Results of a Neo-Adjuvant Bevacizumab, Capecitabine +/- Oxaliplatin and Radiation Multimodality Regimen for Locally Advanced Rectal Cancer
- Author
-
Chiritescu, G., primary, Dumon, K., additional, Vergauwe, P., additional, Arts, J., additional, D'Hoore, A., additional, Debucquoy, A., additional, Verstraete, M., additional, Sagaert, X., additional, Haustermans, K., additional, and Van Cutsem, E., additional
- Published
- 2012
- Full Text
- View/download PDF
57. Diagnostics
- Author
-
Einert, T. R., primary, Schmidt, G., additional, Binnig, G., additional, Balacescu, O., additional, Balacescu, L., additional, Rus, M., additional, Buiga, R., additional, Tudoran, O., additional, Todor, N., additional, Nagy, V., additional, Irimie, A., additional, Neagoe, I., additional, Yacobi, R., additional, Ustaev, E., additional, Berger, R. R., additional, Barshack, I., additional, Kaur, K., additional, Henderson, S., additional, Cutts, A., additional, Domingo, E., additional, Woods, J., additional, Motley, C., additional, Dougherty, B., additional, Middleton, M., additional, Hassan, B., additional, Wang, Y., additional, Beasley, E., additional, Naley, M., additional, Schuh, A., additional, Tomlinson, I., additional, Taylor, J., additional, Planchard, D., additional, Lueza, B., additional, Rahal, A., additional, Lacroix, L., additional, Ngocamus, M., additional, Auger, N., additional, Saulnier, P., additional, Dorfmuller, P., additional, Le Chevalier, T., additional, Celebic, A., additional, Pignon, J. P., additional, Soria, J. C., additional, Besse, B., additional, Sun, Y. H., additional, Wang, R., additional, Li, C. G., additional, Pan, Y. J., additional, Chen, H. Q., additional, Chouchane, L., additional, Shan, J., additional, Kizhakayil, D., additional, Aigha, I., additional, Dsouza, S., additional, Noureddine, B., additional, Gabbouj, S., additional, Mathew, R., additional, Hassen, E., additional, Shan, S., additional, al-Rumaihi, K., additional, al-Bozom, I., additional, al-Said, S., additional, Rabah, D., additional, Farhat, K., additional, Jakobsen Falk, I. A., additional, Green, K. H. Z., additional, Lotfi, K., additional, Fyrberg, A., additional, Pejovic, T., additional, Li, H., additional, Mhawech-Fauceglia, P., additional, Hoatlin, M., additional, Guo, M. G., additional, Huang, M., additional, Ge, Y., additional, Hess, K., additional, Wei, C., additional, Zhang, W., additional, Bogush, T. A., additional, Dudko, E. A., additional, Nureev, M. V., additional, Kamensky, A. A., additional, Polotsky, B. E., additional, Tjulandin, S. A., additional, Davydov, M. I., additional, Caballero, M., additional, Hasmats, J., additional, Green, H., additional, Quanz, M., additional, Buhler, C., additional, Sun, J. S., additional, Dutreix, M., additional, Cebotaru, C. L., additional, Placintar, A. N., additional, Ghilezan, N., additional, Balogh, Z. B., additional, Reiniger, L., additional, Rajnai, H., additional, Csomor, J., additional, Szepesi, A., additional, Balogh, A., additional, Deak, L., additional, Gagyi, E., additional, Bodor, C., additional, Matolcsy, A., additional, Bozhenko, V. K., additional, Rozhkova, N. I., additional, Kudinova, E. A., additional, Bliznyukov, O. P., additional, Vaskevich, E. N., additional, Trotsenko, I. D., additional, Kharchenko, N. V., additional, Kiandarian, I. V., additional, Pulito, C., additional, Terrenato, I., additional, Sacconi, A., additional, Biagioni, F., additional, Mottolese, M., additional, Blandino, G., additional, Muti, P., additional, Falvo, E., additional, Strano, S., additional, Mori, F., additional, Ganci, F., additional, Covello, R., additional, Zoccali, C., additional, Biagini, R., additional, Palmer, G. A., additional, Wegdam, W., additional, Meijer, D., additional, Kramer, G., additional, Langridge, J., additional, Moerland, P. D., additional, de Jong, S. M., additional, Vissers, J. P., additional, Kenter, G. G., additional, Buist, M. R., additional, Aerts, J. M. F. G., additional, Milione, M., additional, de Braud, F., additional, Buzzoni, R., additional, Pusceddu, S., additional, Mazzaferro, V., additional, Damato, A., additional, Pelosi, G., additional, Garassino, M., additional, Broggini, M., additional, Marabese, M., additional, Veronese, S., additional, Ganzinelli, M., additional, Martelli, O., additional, Bossel, N., additional, Fontemaggi, G., additional, Manciocco, V., additional, Sperduti, I., additional, Strigari, L., additional, Spriano, G., additional, Domany, E., additional, Donzelli, S., additional, Bellissimo, T., additional, Alessandrini, G., additional, Carosi, M. A., additional, Pescarmona, E., additional, Facciolo, F., additional, Telera, S., additional, Pompili, A., additional, de Vriendt, V., additional, de Roock, W., additional, di Narzo, A. F., additional, Tian, S., additional, Biesmans, B., additional, Jacobs, B., additional, de Schutter, J., additional, Budzinska, E., additional, Sagaert, X., additional, Delorenzi, M., additional, Simon, I., additional, Tejpar, S., additional, Zhu, Y., additional, Wang, H. K., additional, Ye, D. W., additional, Denisov, E., additional, Tsyganov, M., additional, Tashireva, L., additional, Zavyalova, M., additional, Perelmuter, V., additional, Cherdyntseva, N., additional, Kim, Y. C., additional, Jang, T., additional, Oh, I. J., additional, Kim, K. S., additional, Ban, H., additional, Na, K. J., additional, Ahn, S. J., additional, Kang, H., additional, Kim, W. J., additional, Park, C., additional, Abousamra, N. K., additional, El-Din, M. S., additional, and Azmy, E. A., additional
- Published
- 2012
- Full Text
- View/download PDF
58. P1.28 Dusp4 Expression as A Marker of Heterogeneous Signaling in Colorectal Cancer Patients
- Author
-
de Vriendt, V., primary, de Roock, W., additional, di Narzo, A.F., additional, Tian, S., additional, Biesmans, B., additional, Jacobs, B., additional, de Schutter, J., additional, Budzinska, E., additional, Sagaert, X., additional, Delorenzi, M., additional, Simon, I., additional, and Tejpar, S., additional
- Published
- 2012
- Full Text
- View/download PDF
59. PD-0568 PHASE II STUDY OF NEO ADJUVANT TREATMENT WITH AVASTIN, XELODA AND ELOXATIN IN RECTAL CANCER (AXE BEAM)
- Author
-
Debucquoy, A., primary, Verstraete, M., additional, Chiritescu, G., additional, Dumon, K., additional, Vergauwe, P., additional, Machiels, J.P., additional, Penninckx, F., additional, Sagaert, X., additional, Van Cutsem, E., additional, and Haustermans, K., additional
- Published
- 2012
- Full Text
- View/download PDF
60. t(X;14)(p11.4;q32.33) is recurrent in marginal zone lymphoma and up-regulates GPR34
- Author
-
Baens, M., primary, Finalet Ferreiro, J., additional, Tousseyn, T., additional, Urbankova, H., additional, Michaux, L., additional, de Leval, L., additional, Dierickx, D., additional, Wolter, P., additional, Sagaert, X., additional, Vandenberghe, P., additional, De Wolf-Peeters, C., additional, and Wlodarska, I., additional
- Published
- 2011
- Full Text
- View/download PDF
61. PC.1.5: CONFOCAL LASER ENDOMICROSCOPY IN BARRETT'S ESOPHAGUS: INTEROBSERVER AGREEMENT AND ACCURACY AMONG AN INTERNATIONAL GROUP OF GASTROENTEROLOGISTS AND PATHOLOGISTS
- Author
-
Trovato, C., primary, Bisschops, R., additional, Goetz, M., additional, Sonzogni, A., additional, Vieth, M., additional, Sagaert, X., additional, Tamayo, D., additional, and Crosta, C., additional
- Published
- 2011
- Full Text
- View/download PDF
62. Subclinical GvHD in non-irradiated F1 hybrids: severe lymphoid-tissue GvHD causing prolonged immune dysfunction
- Author
-
Sprangers, B, primary, Van Wijmeersch, B, additional, Luyckx, A, additional, Sagaert, X, additional, Verbinnen, B, additional, Rutgeerts, O, additional, Lenaerts, C, additional, Tousseyn, T, additional, Dubois, B, additional, Waer, M, additional, and Billiau, A D, additional
- Published
- 2010
- Full Text
- View/download PDF
63. Microarray ANALYSIS of t(11;18)(Q21;Q21)-positive and -negative gastrointestinal MALT lymphomas.
- Author
-
Sagaert, X., primary, Van Cutsem, E., additional, De Hertogh, G., additional, Van Loo, P., additional, De Wolf-Peeters, C., additional, Geboes, K., additional, and Tousseyn, T., additional
- Published
- 2010
- Full Text
- View/download PDF
64. Analysis of prognostic value of biomarkers in gastric MALT lymphomas.
- Author
-
Tousseyn, T., primary, Haesevoets, E., additional, Geboes, K., additional, De Hertogh, G., additional, Van Cutsem, E., additional, and Sagaert, X., additional
- Published
- 2010
- Full Text
- View/download PDF
65. Allogeneic bone marrow transplantation and donor lymphocyte infusion in a mouse model of irradiation-induced myelodysplastic/myeloproliferation syndrome (MD/MPS): evidence for a graft-versus-MD/MPS effect
- Author
-
Sprangers, B, primary, Van Wijmeersch, B, additional, Luyckx, A, additional, Sagaert, X, additional, De Somer, L, additional, Rutgeerts, O, additional, Lenaerts, C, additional, Landuyt, W, additional, Boeckx, N, additional, Dubois, B, additional, De Wolf-Peeters, C, additional, Waer, M, additional, and Billiau, A D, additional
- Published
- 2008
- Full Text
- View/download PDF
66. Anaplastic large cell lymphoma
- Author
-
Sagaert, X, primary and De Wolf-Peeters, C, additional
- Published
- 2003
- Full Text
- View/download PDF
67. 579P - Final Results of a Randomized Phase Ii Study with Neo-Adjuvant Triplet or Doublet Therapy, Radiation and Total Mesorectal Excision for Locally Advanced Rectal Cancer: Axe Beam
- Author
-
Chiritescu, G., Dumon, K., Vergauwe, P., Arts, J., Verbeke, L., Polus, M., Humblet, Y., van Laethem, J., Daisne, J., Decaestecker, J., D'Hoore, A., Mardjuadi, F., Debucquoy, A., Verstraete, M., Sagaert, X., Haustermans, K., and Van Cutsem, E.
- Published
- 2014
- Full Text
- View/download PDF
68. O-0010 - AXE Beam: Neo-Adjuvant Triplet Versus Doublet Therapy with Radiation and Total Mesorectal Excision for Locally Advanced Rectal Cancer – A Randomized Phase II Study at the End of Recruitment
- Author
-
Chiritescu, G., Dumon, K., Vergauwe, P., Arts, J., Verbeke, L., Polus, M., Humblet, Y., Van Laethem, J.L., Daisne, J.F., Decaestecker, J., D'Hoore, A., Mardjuadi, F., Debucquoy, A., Verstraete, M., Sagaert, X., Haustermans, K., and Van Cutsem, E.
- Published
- 2014
- Full Text
- View/download PDF
69. An unsuspected cause of diarrhoea and gastrointestinal bleeding during corticosteroid therapy.
- Author
-
Vanuytsel, T., Sagaert, X., Van Dijck, H., Vandepitte, K., Shea-Donohue, T., Tack, J., and Van den Brande, P.
- Published
- 2014
70. SODIUM THIOSULPHATE IN THE TREATMENT OF CALCIFIC UREMIC ARTERIOLOPATHY: FRIEND OR FOE?
- Author
-
Vanparys, J., Ben Sprangers, Sagaert, X., and Kuypers, D.
71. In-depth characterization of the tumor microenvironment in central nervous system lymphoma reveals implications for immune-checkpoint therapy
- Author
-
Giorgio Cattoretti, Lukas Marcelis, Thomas Tousseyn, Daan Dierickx, Anne-Marie Delsupehe, Pauline Biesemans, Gregor Verhoef, Francesca Maria Bosisio, Olivier Gheysens, Xavier Sagaert, Peter Vandenberghe, Koen Debackere, Julio Finalet Ferreiro, Asier Antoranz, Marcelis, L, Antoranz, A, Delsupehe, A, Biesemans, P, Ferreiro, J, Debackere, K, Vandenberghe, P, Verhoef, G, Gheysens, O, Cattoretti, G, Bosisio, F, Sagaert, X, Dierickx, D, and Tousseyn, T
- Subjects
Male ,Herpesvirus 4, Human ,Cancer Research ,Lymphoma ,medicine.medical_treatment ,CD8-Positive T-Lymphocytes ,Central Nervous System Neoplasms ,0302 clinical medicine ,hemic and lymphatic diseases ,Tumor Microenvironment ,Immunology and Allergy ,Cytotoxic T cell ,Primary central nervous system lymphoma ,Child ,Aged, 80 and over ,Middle Aged ,medicine.anatomical_structure ,Oncology ,Female ,Immunotherapy ,TILS ,Adult ,Adolescent ,T cell ,Immunology ,Antigens, Differentiation, Myelomonocytic ,Receptors, Cell Surface ,Young Adult ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,Antigens, CD ,Biomarkers, Tumor ,medicine ,Humans ,PCNSL ,Aged ,Retrospective Studies ,Tumor microenvironment ,business.industry ,TME ,medicine.disease ,Immune checkpoint ,Cancer research ,business ,CD8 ,T-Lymphocytes, Cytotoxic ,030215 immunology - Abstract
Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin lymphoma with an aggressive clinical course. To investigate the potential of immune-checkpoint therapy, we retrospectively studied the tumor microenvironment (TME) using high-plex immunohistochemistry in 22 PCNSL and compared to 7 secondary CNS lymphomas (SCNSL) and 7 "other" CNSL lymphomas with the presence of the Epstein-Barr virus and/or compromised immunity. The TME in PCNSL was predominantly composed of CD8+ cytotoxic T cells and CD163+ phagocytes. Despite molecular differences between PCNSL and SCNSL, the cellular composition and the functional spectrum of cytotoxic T cells were similar. But cytotoxic T cell activation was significantly influenced by pre-biopsy corticosteroids intake, tumor expression of PD-L1 and the presence of EBV. The presence of low numbers of CD8+ T cells and geographic-type necrosis each predicted inferior outcome in PCNSL. Both M1-like (CD68 + CD163low) and M2-like (CD68 + CD163high) phagocytes were identified, and an increased ratio of M1-like/M2-like phagocytes was associated with a better survival. PD-L1 was expressed in lymphoma cells in 28% of cases, while PD1 was expressed in only 0.4% of all CD8+ T cells. TIM-3, a marker for T cell exhaustion, was significantly more expressed in CD8posPD-1pos T cells compared to CD8posPD-1neg T cells, and a similar increased expression was observed in M2-like pro-tumoral phagocytes. In conclusion, the clinical impact of TME composition supports the use of immune-checkpoint therapies in PCNSL. Based on observed differences in immune-checkpoint expression, combinations that boost cytotoxic T cell activation (by blocking TIM-3 or TGFBR1) prior to the administration of PD-L1 inhibition could be of interest.
- Published
- 2020
72. Prevalence of Achromobacter xylosoxidans in pulmonary mucosa-associated lymphoid tissue lymphoma in different regions of Europe
- Author
-
Patrick Adam, Perikles Kosmidis, Piotr Czapiewski, Ming-Qing Du, Giancarlo Pruneri, Falko Fend, Claudio Agostinelli, Alicia Morresi-Hauf, Xavier Sagaert, Giovanni Martinelli, Thomas Tousseyn, Ludmila Boudova, Seba Colak, Krzysztof Okoń, Stefano Pileri, Adam P, Czapiewski P, Colak S, Kosmidis P, Tousseyn T, Sagaert X, Boudova L, Okoń K, Morresi-Hauf A, Agostinelli C, Pileri S, Pruneri G, Martinelli G, Du MQ, and Fend F
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Achromobacter ,Adolescent ,Prevalence ,Pathogenesis ,Young Adult ,immune system diseases ,hemic and lymphatic diseases ,LYMPHOMA ,medicine ,Humans ,Amino Acid Sequence ,Aged ,Aged, 80 and over ,biology ,Achromobacter denitrificans ,MALT lymphoma ,Lymphoma, B-Cell, Marginal Zone ,Hematology ,Achromobacter xylosoxidans ,Middle Aged ,biology.organism_classification ,medicine.disease ,Lymphoma ,Europe ,Lymphatic system ,Immunology ,Female ,Gram-Negative Bacterial Infections - Abstract
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) comprises 7-8% of B-cell lymphomas and commonly originates from a background of long-standing chronic inflammation. An association with distinct bacteria species has been confirmed for several anatomical sites of MALT lymphoma. For pulmonary MALT lymphoma, however, a clear link with an infectious agent or autoimmune disorder has not yet been reported. Using a 16S rRNA gene-based approach, we have recently identified Achromobacter (Alcaligenes) xylosoxidans in eight of nine cases of pulmonary MALT lymphoma. A. xylosoxidans is a gram-negative betaproteobacterium with low virulence, but high resistance to antibiotic treatment. To further examine a potential association with A. xylosoxidans, 124 cases of pulmonary MALT lymphoma and 82 control tissues from six European countries were analysed using a specific nested PCR. Although prevalence rates for A. xylosoxidans varied significantly from country to country, they were consistently higher for MALT lymphoma as compared to controls. Overall, 57/124 (46%) pulmonary MALT lymphomas and 15/82 (18%) control tissues were positive for A. xylosoxidans (P = 0·004). Whether the significant association of A. xylosoxidans with pulmonary MALT lymphoma demonstrated in our study points to a potential causal role in the pathogenesis of this lymphoma will require further studies.
- Published
- 2014
73. Nodular lymphocyte predominant hodgkin lymphoma and T cell/histiocyte rich large B cell lymphoma--endpoints of a spectrum of one disease?
- Author
-
Thomas Tousseyn, Martin-Leo Hansmann, Claudia Döring, Xavier Sagaert, Christian Steidl, Chris De Wolf-Peeters, Sebastian Newrzela, Ralf Küppers, Randy D. Gascoyne, Maurilio Ponzoni, Benjamin Rengstl, Fabio Facchetti, Sylvia Hartmann, Christina Jakobus, Hartmann, S, Döring, C, Jakobus, C, Rengstl, B, Newrzela, S, Tousseyn, T, Sagaert, X, Ponzoni, Maurilio, Facchetti, F, de Wolf Peeters, C, Steidl, C, Gascoyne, R, Küppers, R, and Hansmann, Ml
- Subjects
Male ,Pathology ,medicine.medical_specialty ,T cell ,Medizin ,lcsh:Medicine ,Disease ,Biology ,Lymphoma, T-Cell ,medicine ,Humans ,Lymphocytes ,ddc:610 ,lcsh:Science ,Lymphoma, Follicular ,Histiocyte ,Regulation of gene expression ,Tumor microenvironment ,Multidisciplinary ,Gene Expression Profiling ,lcsh:R ,medicine.disease ,Hodgkin Disease ,Neoplasm Proteins ,Lymphoma ,Gene Expression Regulation, Neoplastic ,Gene expression profiling ,medicine.anatomical_structure ,Nodular Lymphocyte Predominant Hodgkin Lymphoma ,Pediatrics, Perinatology and Child Health ,Immunohistochemistry ,Female ,lcsh:Q ,Lymphoma, Large B-Cell, Diffuse ,T-Cell/Histiocyte-Rich Large B-Cell Lymphoma ,Research Article - Abstract
In contrast to the commonly indolent clinical behavior of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), T cell/histiocyte rich large B cell lymphoma (THRLBCL) is frequently diagnosed in advanced clinical stages and has a poor prognosis. Besides the different clinical presentations of these lymphoma entities, there are variants of NLPHL with considerable histopathologic overlap compared to THRLBCL. Especially THRLBCL-like NLPHL, a diffuse form of NLPHL, often presents a histopathologic pattern similar to THRLBCL, suggesting a close relationship between both lymphoma entities. To corroborate this hypothesis, we performed gene expression profiling of microdissected tumor cells of NLPHL, THRLBCL-like NLPHL and THRLBCL. In unsupervised analyses, the lymphomas did not cluster according to their entity. Moreover, even in supervised analyses, very few consistently differentially expressed transcripts were found, and for these genes the extent of differential expression was only moderate. Hence, there are no clear and consistent differences in the gene expression of the tumor cells of NLPHL, THRLBCL-like NLPHL and THRLBCL. Based on the gene expression studies, we identified BAT3/BAG6, HIGD1A, and FAT10/UBD as immunohistochemical markers expressed in the tumor cells of all three lymphomas. Characterization of the tumor microenvironment for infiltrating T cells and histiocytes revealed significant differences in the cellular composition between typical NLPHL and THRLBCL cases. However, THRLBCL-like NLPHL presented a histopathologic pattern more related to THRLBCL than NLPHL. In conclusion, NLPHL and THRLBCL may represent a spectrum of the same disease. The different clinical behavior of these lymphomas may be strongly influenced by differences in the lymphoma microenvironment, possibly related to the immune status of the patient at the timepoint of diagnosis. © 2013 Hartmann et al. OA gold
- Published
- 2013
74. Intrapatient Cetuximab Dose Escalation in Metastatic Colorectal Cancer According to the Grade of Early Skin Reactions: The Randomized EVEREST Study
- Author
-
Markus Moehler, M. Schlichting, Eric Van Cutsem, Jan B. Vermorken, Soetkin Vlassak, Hans Gelderblom, Bengt Glimelius, Frédéric Viret, Yves Humblet, Dirk Vanbeckevoort, Xavier Sagaert, Elisa Gallerani, Sabine Tejpar, Marc Peeters, Fortunato Ciardiello, Annemieke Cats, A. Hendlisz, Van Cutsem, E, Tejpar, S, Vanbeckevoort, D, Peeters, M, Humblet, Y, Gelderblom, H, Vermorken, Jb, Viret, F, Glimelius, B, Gallerani, E, Hendlisz, A, Cats, A, Moehler, M, Sagaert, X, Vlassak, S, Schlichting, M, and Ciardiello, Fortunato
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,Population ,Cetuximab ,medicine.disease_cause ,Antibodies, Monoclonal, Humanized ,Irinotecan ,Gastroenterology ,Pharmacokinetics ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Dosing ,Adverse effect ,education ,neoplasms ,Aged ,education.field_of_study ,Dose-Response Relationship, Drug ,business.industry ,Antibodies, Monoclonal ,Middle Aged ,digestive system diseases ,Surgery ,Oncology ,Fluorouracil ,Camptothecin ,Female ,Human medicine ,KRAS ,Drug Eruptions ,business ,Colorectal Neoplasms ,medicine.drug - Abstract
Purpose Skin toxicity in patients receiving cetuximab has been associated positively with clinical outcome in several tumor types. This study investigated the effect of cetuximab dose escalation in patients with irinotecan-refractory metastatic colorectal cancer who had developed no or mild skin reactions after 21 days of treatment at the standard dose. This article reports clinical and pharmacokinetic (PK) data. Patients and Methods After 21 days of standard-dose cetuximab (400 mg/m2 initial dose, then 250 mg/m2 per week) plus irinotecan, patients with ≤ grade 1 skin reactions were randomly assigned to standard-dose (group A) or dose-escalated (to 500 mg/m2 per week; group B) cetuximab. Patients with ≥ grade 2 skin reactions continued on standard-dose cetuximab plus irinotecan (group C). Results The intent-to-treat population comprised 157 patients. PK profiles reflected the dose increase and were predictable across the dose range investigated. Weekly cetuximab doses of up to 500 mg/m2 were well tolerated, and grade 3 and 4 adverse events were generally comparable between treatment groups. Dose escalation (n = 44) was associated with an increase in skin reactions ≥ grade 2 compared with standard (n = 45) dosing (59% v 38%, respectively). Dose escalation, compared with standard dosing, showed some evidence for improved response rate (30% v 16%, respectively) and disease control rate (70% v 58%, respectively) but no indication of benefit in relation to overall survival. In an exploratory analysis, dose escalation seemed to increase response rate compared with standard dosing in patients with KRAS wild-type but not KRAS mutant tumors. Conclusion Cetuximab serum concentrations increased predictably with dose. Higher dose levels were well tolerated. The possible indication for improved efficacy in the dose-escalation group warrants further investigation.
- Published
- 2012
75. 419 - Expression profiling of tumour budding cells in colorectal cancer suggests an EMT-like phenotype and molecular subtype switching.
- Author
-
De Smedt, L., Palmans, S., Govaere, O., Wouters, J., Barras, D., Dekervel, J., Tejpar, S., Lambrechts, D., and Sagaert, X.
- Published
- 2016
- Full Text
- View/download PDF
76. A cheesy diagnosis.
- Author
-
Wisanto E, D'Hondt M, Aerts R, Geboes K, De Hertogh G, and Sagaert X
- Published
- 2010
- Full Text
- View/download PDF
77. MetDecode: methylation-based deconvolution of cell-free DNA for noninvasive multi-cancer typing.
- Author
-
Passemiers A, Tuveri S, Sudhakaran D, Jatsenko T, Laga T, Punie K, Hatse S, Tejpar S, Coosemans A, Van Nieuwenhuysen E, Timmerman D, Floris G, Van Rompuy AS, Sagaert X, Testa A, Ficherova D, Raimondi D, Amant F, Lenaerts L, Moreau Y, and Vermeesch JR
- Subjects
- Humans, DNA Methylation, Neoplasms genetics, Cell-Free Nucleic Acids blood, Algorithms, Biomarkers, Tumor blood
- Abstract
Motivation: Circulating-cell free DNA (cfDNA) is widely explored as a noninvasive biomarker for cancer screening and diagnosis. The ability to decode the cells of origin in cfDNA would provide biological insights into pathophysiological mechanisms, aiding in cancer characterization and directing clinical management and follow-up., Results: We developed a DNA methylation signature-based deconvolution algorithm, MetDecode, for cancer tissue origin identification. We built a reference atlas exploiting de novo and published whole-genome methylation sequencing data for colorectal, breast, ovarian, and cervical cancer, and blood-cell-derived entities. MetDecode models the contributors absent in the atlas with methylation patterns learnt on-the-fly from the input cfDNA methylation profiles. In addition, our model accounts for the coverage of each marker region to alleviate potential sources of noise. In-silico experiments showed a limit of detection down to 2.88% of tumor tissue contribution in cfDNA. MetDecode produced Pearson correlation coefficients above 0.95 and outperformed other methods in simulations (P < 0.001; T-test; one-sided). In plasma cfDNA profiles from cancer patients, MetDecode assigned the correct tissue-of-origin in 84.2% of cases. In conclusion, MetDecode can unravel alterations in the cfDNA pool components by accurately estimating the contribution of multiple tissues, while supplied with an imperfect reference atlas., Availability and Implementation: MetDecode is available at https://github.com/JorisVermeeschLab/MetDecode., (© The Author(s) 2024. Published by Oxford University Press.)
- Published
- 2024
- Full Text
- View/download PDF
78. Single cell dynamics of tumor specificity vs bystander activity in CD8 + T cells define the diverse immune landscapes in colorectal cancer.
- Author
-
Borràs DM, Verbandt S, Ausserhofer M, Sturm G, Lim J, Verge GA, Vanmeerbeek I, Laureano RS, Govaerts J, Sprooten J, Hong Y, Wall R, De Hertogh G, Sagaert X, Bislenghi G, D'Hoore A, Wolthuis A, Finotello F, Park WY, Naulaerts S, Tejpar S, and Garg AD
- Abstract
CD8
+ T cell activation via immune checkpoint blockade (ICB) is successful in microsatellite instable (MSI) colorectal cancer (CRC) patients. By comparison, the success of immunotherapy against microsatellite stable (MSS) CRC is limited. Little is known about the most critical features of CRC CD8+ T cells that together determine the diverse immune landscapes and contrasting ICB responses. Hence, we pursued a deep single cell mapping of CRC CD8+ T cells on transcriptomic and T cell receptor (TCR) repertoire levels in a diverse patient cohort, with additional surface proteome validation. This revealed that CRC CD8+ T cell dynamics are underscored by complex interactions between interferon-γ signaling, tumor reactivity, TCR repertoire, (predicted) TCR antigen-specificities, and environmental cues like gut microbiome or colon tissue-specific 'self-like' features. MSI CRC CD8+ T cells showed tumor-specific activation reminiscent of canonical 'T cell hot' tumors, whereas the MSS CRC CD8+ T cells exhibited tumor unspecific or bystander-like features. This was accompanied by inflammation reminiscent of 'pseudo-T cell hot' tumors. Consequently, MSI and MSS CRC CD8+ T cells showed overlapping phenotypic features that differed dramatically in their TCR antigen-specificities. Given their high discriminating potential for CD8+ T cell features/specificities, we used the single cell tumor-reactive signaling modules in CD8+ T cells to build a bulk tumor transcriptome classification for CRC patients. This "Immune Subtype Classification" (ISC) successfully distinguished various tumoral immune landscapes that showed prognostic value and predicted immunotherapy responses in CRC patients. Thus, we deliver a unique map of CRC CD8+ T cells that drives a novel tumor immune landscape classification, with relevance for immunotherapy decision-making., (© 2023. The Author(s).)- Published
- 2023
- Full Text
- View/download PDF
79. Hemicolectomy versus appendectomy for patients with appendiceal neuroendocrine tumours 1-2 cm in size: a retrospective, Europe-wide, pooled cohort study.
- Author
-
Nesti C, Bräutigam K, Benavent M, Bernal L, Boharoon H, Botling J, Bouroumeau A, Brcic I, Brunner M, Cadiot G, Camara M, Christ E, Clerici T, Clift AK, Clouston H, Cobianchi L, Ćwikła JB, Daskalakis K, Frilling A, Garcia-Carbonero R, Grozinsky-Glasberg S, Hernando J, Hervieu V, Hofland J, Holmager P, Inzani F, Jann H, Jimenez-Fonseca P, Kaçmaz E, Kaemmerer D, Kaltsas G, Klimacek B, Knigge U, Kolasińska-Ćwikła A, Kolb W, Kos-Kudła B, Kunze CA, Landolfi S, La Rosa S, López CL, Lorenz K, Matter M, Mazal P, Mestre-Alagarda C, Del Burgo PM, van Dijkum EJMN, Oleinikov K, Orci LA, Panzuto F, Pavel M, Perrier M, Reims HM, Rindi G, Rinke A, Rinzivillo M, Sagaert X, Satiroglu I, Selberherr A, Siebenhüner AR, Tesselaar MET, Thalhammer MJ, Thiis-Evensen E, Toumpanakis C, Vandamme T, van den Berg JG, Vanoli A, van Velthuysen MF, Verslype C, Vorburger SA, Lugli A, Ramage J, Zwahlen M, Perren A, and Kaderli RM
- Subjects
- Male, Humans, Female, Adult, Appendectomy adverse effects, Appendectomy methods, Retrospective Studies, Cohort Studies, Lymphatic Metastasis, Europe, Colectomy adverse effects, Neuroendocrine Tumors surgery, Neuroendocrine Tumors pathology, Appendiceal Neoplasms surgery, Appendiceal Neoplasms diagnosis, Appendiceal Neoplasms pathology
- Abstract
Background: Awareness of the potential global overtreatment of patients with appendiceal neuroendocrine tumours (NETs) of 1-2 cm in size by performing oncological resections is increasing, but the rarity of this tumour has impeded clear recommendations to date. We aimed to assess the malignant potential of appendiceal NETs of 1-2 cm in size in patients with or without right-sided hemicolectomy., Methods: In this retrospective cohort study, we pooled data from 40 hospitals in 15 European countries for patients of any age and Eastern Cooperative Oncology Group performance status with a histopathologically confirmed appendiceal NET of 1-2 cm in size who had a complete resection of the primary tumour between Jan 1, 2000, and Dec 31, 2010. Patients either had an appendectomy only or an appendectomy with oncological right-sided hemicolectomy or ileocecal resection. Predefined primary outcomes were the frequency of distant metastases and tumour-related mortality. Secondary outcomes included the frequency of regional lymph node metastases, the association between regional lymph node metastases and histopathological risk factors, and overall survival with or without right-sided hemicolectomy. Cox proportional hazards regression was used to estimate the relative all-cause mortality hazard associated with right-sided hemicolectomy compared with appendectomy alone. This study is registered with ClinicalTrials.gov, NCT03852693., Findings: 282 patients with suspected appendiceal tumours were identified, of whom 278 with an appendiceal NET of 1-2 cm in size were included. 163 (59%) had an appendectomy and 115 (41%) had a right-sided hemicolectomy, 110 (40%) were men, 168 (60%) were women, and mean age at initial surgery was 36·0 years (SD 18·2). Median follow-up was 13·0 years (IQR 11·0-15·6). After centralised histopathological review, appendiceal NETs were classified as a possible or probable primary tumour in two (1%) of 278 patients with distant peritoneal metastases and in two (1%) 278 patients with distant metastases in the liver. All metastases were diagnosed synchronously with no tumour-related deaths during follow-up. Regional lymph node metastases were found in 22 (20%) of 112 patients with right-sided hemicolectomy with available data. On the basis of histopathological risk factors, we estimated that 12·8% (95% CI 6·5 -21·1) of patients undergoing appendectomy probably had residual regional lymph node metastases. Overall survival was similar between patients with appendectomy and right-sided hemicolectomy (adjusted hazard ratio 0·88 [95% CI 0·36-2·17]; p=0·71)., Interpretation: This study provides evidence that right-sided hemicolectomy is not indicated after complete resection of an appendiceal NET of 1-2 cm in size by appendectomy, that regional lymph node metastases of appendiceal NETs are clinically irrelevant, and that an additional postoperative exclusion of metastases and histopathological evaluation of risk factors is not supported by the presented results. These findings should inform consensus best practice guidelines for this patient cohort., Funding: Swiss Cancer Research foundation., Competing Interests: Declaration of interests MBe reports funding from Novartis, Pfizer, and Ipsen; payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Novartis, Pfizer, Ipsen, and Advanced Accelerator Applications (AAA); support for attending meetings or travel from Novartis, Pfizer, and Ipsen; and participation on data safety monitoring board or advisory boards from Pfizer and AAA. IB reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Bristol Myers Squibb (BMS) and Bayer Vital and support for attending meetings or travel for European Musculo-Skeletal Oncology Society 2022 conference from PharmaMar. RG-C reports funding of investigator-initiated clinical trials from Pfizer, BMS, and MSD, and an real-world data project from Servier; consulting fees from AAA/Novartis, Advanz Pharma, Amgen, Bayer, BMS, Boehringer (Ingelheim), Esteve, Hutchmed, Ipsen, Merck, Midatech Pharma, MSD, PharmaMar, and Pierre Fabre; and payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Roche. GC reports grants or contracts from AAA; consulting fees from AAA; payments or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from AAA, Ipsen, and Keocyt; and support for attending meetings or travel from AAA, Ipsen, and Keocyt. MPa reports payments for advisory boards or lectures from AAA and Novartis; payments for advisory boards, consultancy, or lectures from Ipsen; payment for lectures from Boehringer Ingelheim, MSD, Lilly, and Recordati; payment for advisory boards from Riemser; payment for services (radiological review of phase 3 study) from Hutchmed; payment for travel for participation in study steering committee meeting from Rayzebio; payment to institution from Crinetics and AAA; and unpaid roles as ENETS vice president, European Society for Medical Oncology (ESMO) Education Committee, ESMO scientific steering committee NET track, advisor on the International Neuroendocrine Cancer Alliance board, and advisor for German patient support group. GR reports payments for speaker bureaus from AAA. AR reports being an ENETS Advisory Board member. TV reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Ipsen; support for attending meetings or travel from Ipsen; and an unpaid position as secretary in the Dutch Belgian Neuroendocrine Tumor Society. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
80. Nonoperative versus operative approach according to the response to neoadjuvant chemoradiotherapy for rectal cancer: A prospective cohort study.
- Author
-
Bulens PP, Smets L, Debucquoy A, Joye I, D'Hoore A, Wolthuis A, Debrun L, Dekervel J, Van Cutsem E, Dresen R, Vandecaveye V, Deroose CM, Sagaert X, and Haustermans K
- Abstract
Purpose: To report on organ preservation following chemoradiotherapy (CRT) in a prospective cohort of locally advanced rectal cancer patients., Methods and Materials: Fifty-two patients received CRT. MRI and
18 F-FDG-PET/CT were performed prior to CRT. Response assessment was done 6 and 12 weeks after CRT using digital rectal examination, MRI,18 F-FDG-PET/CT and endoscopy. For clinical complete response or minimal residual disease, a watch-and-wait (W&W) protocol was started.Regrowth-free survival (ReFS), Total Mesorectal Excision-free disease-free survival, distant metastasis-free survival (DMFS) and overall survival (OS) were evaluated using Kaplan-Meier method. Functional outcome was compared with the Wilcoxon signed-rank test using EORTC QLQ-C30, MSKCC BFI, LARS and IIEF-5/FSFI-5 questionnaires. A previously developed prediction model performance was tested using receiver operating characteristic analysis., Results: 29/52 patients entered a W&W protocol. There was no difference in two-year DMFS (81.1 % vs 78.8 %, p = 0.82), two-year OS (96.4 % vs 100 %, p = 0.38) and two-year DFS (77.5 % vs 78.8 %, p = 0.87) between W&W patients and those who underwent surgery at 12 weeks after CRT. Two-year DMFS differed between W&W with local regrowth, W&W with sustained response and patients who had surgery (66.7 % vs 88.0 % vs 78.8 %; p = 0.04). At 6 and 12 months, W&W patients reported good QoL and bowel function. The model validation reached an AUC of 0.627., Conclusion: Good functional outcome in patients with rectal cancer allocated to surveillance after CRT needs to be balanced against potentially worse DMFS in a subset of patients without sustained clinical complete response. Reliable prediction of patients eligible for surveillance programs needs further investigation., Competing Interests: 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., (© 2022 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)- Published
- 2022
- Full Text
- View/download PDF
81. Esophageal Cancer in Epiphrenic Diverticulum With Fistulization to the Lung.
- Author
-
Vanstraelen S, Depypere L, Sagaert X, Nafteux P, and Ceulemans LJ
- Published
- 2022
- Full Text
- View/download PDF
82. Importance of Lymph Node Response After Neoadjuvant Chemoradiotherapy for Esophageal Adenocarcinoma.
- Author
-
Depypere L, De Hertogh G, Moons J, Provoost AL, Lerut T, Sagaert X, Coosemans W, Van Veer H, and Nafteux P
- Subjects
- Adenocarcinoma diagnosis, Adenocarcinoma secondary, Aged, Belgium epidemiology, Biopsy, Fine-Needle methods, Chemoradiotherapy, Adjuvant methods, Endoscopy, Gastrointestinal methods, Endosonography, Esophageal Neoplasms diagnosis, Esophageal Neoplasms mortality, Esophageal Neoplasms secondary, Female, Follow-Up Studies, Humans, Lymph Nodes drug effects, Lymph Nodes radiation effects, Lymphatic Metastasis, Male, Middle Aged, Retrospective Studies, Survival Rate trends, Adenocarcinoma therapy, Esophageal Neoplasms therapy, Esophagectomy methods, Lymph Nodes pathology, Neoplasm Staging
- Abstract
Background: Tumor response and lymph node involvement are the most important prognosticators in resected patients with esophageal adenocarcinoma after neoadjuvant chemoradiotherapy (nCRT). We hypothesize that lymph node response (LNR) is also a valuable prognosticator in these patients, potentially revealing the added effect of nCRT., Methods: Hematoxylin and eosin slides of 193 esophageal adenocarcinoma patients with clinical suspicion of lymph node involvement (cN+) and treated with nCRT between 2008 and 2015 were assessed. Lymph nodes containing viable tumor cells were considered ypN+, and those negative for viable tumor were ypN0. LNR was also described according to an earlier defined method. Three groups were obtained: ypN0/LNR-, ypN0/LNR+, and ypN+. They were compared with 188 cN+ patients being pN0 (n = 45) or pN+ (n = 143) after upfront esophageal resection., Results: Forty-four patients were ypN0/LNR-, 55 were ypN0/LNR+, and 94 were ypN+. Median overall survival was 96.4, 31.2, and 20.6 months, respectively, and was significantly different between ypN0/LNR- and ypN0/LNR+ groups (P = .020). Survival was comparable between ypN0/LNR- and pN0 (104.2 months) groups (P = .519) and between ypN+ and pN+ (21.6 months) groups (P = .966). In ypN0 patients, risk of death in LNR+ patients was tripled compared with LNR- patients., Conclusions: In cN+ esophageal adenocarcinoma patients treated with nCRT with postoperative final pathology being ypN0, median overall survival is tripled when no signs of LNR were found and comparable to cN+/pN0 upfront esophagectomy patients, suggesting that 23% of patients treated with nCRT were in fact true N0 and overtreated by nCRT. ypN+ patients have no survival benefit compared with pN+ patients., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
83. 68Ga-DOTATATE PET/CT Distinguishes Neuroendocrine Tumor Mesenteric Lymph Node Metastasis From an Extensive IgG4-Positive Fibrosis Surrounding It.
- Author
-
Ahmadi Bidakhvidi N, Cuyle PJ, Sagaert X, Ballaux F, and Deroose CM
- Subjects
- Female, Fibrosis, Humans, Immunoglobulin G, Lymphatic Metastasis, Middle Aged, Positron Emission Tomography Computed Tomography, Neuroendocrine Tumors diagnostic imaging, Organometallic Compounds
- Abstract
Abstract: A 56-year-old woman presented with right iliac fossa pain. Abdominal CT showed a mesenteric mass in the right iliac fossa, adjacent to the vena cava inferior and right ureter. Biopsy of the mass revealed a well-differentiated neuroendocrine tumor. 68Ga-DOTATATE PET/CT showed strong somatostatin receptor expression only within in a small, central area of this mesenteric mass, with faint 68Ga-DOTATATE uptake in the majority of this mesenteric mass. Pathology revealed an IgG4-positive storiform fibrosis surrounding a mesenteric adenopathy. 68Ga-DOTATATE PET/CT discriminates between neuroendocrine tumor lymph node metastases and fibrosis, hereby avoiding potential sampling error of tumor biopsies and guiding surgical approach., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
84. Correction to: In-depth characterization of the tumor microenvironment in central nervous system lymphoma reveals implications for immune-checkpoint therapy.
- Author
-
Marcelis L, Antoranz A, Delsupehe AM, Biesemans P, Ferreiro JF, Debackere K, Vandenberghe P, Verhoef G, Clement P, De Vleeschouwer S, Gheysens O, Cattoretti G, Bosisio FM, Sagaert X, Dierickx D, and Tousseyn T
- Published
- 2021
- Full Text
- View/download PDF
85. In-depth characterization of the tumor microenvironment in central nervous system lymphoma reveals implications for immune-checkpoint therapy.
- Author
-
Marcelis L, Antoranz A, Delsupehe AM, Biesemans P, Ferreiro JF, Debackere K, Vandenberghe P, Verhoef G, Gheysens O, Cattoretti G, Bosisio FM, Sagaert X, Dierickx D, and Tousseyn T
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Antigens, CD immunology, Antigens, Differentiation, Myelomonocytic immunology, Biomarkers, Tumor immunology, CD8-Positive T-Lymphocytes immunology, Central Nervous System Neoplasms virology, Child, Female, Herpesvirus 4, Human pathogenicity, Humans, Lymphocytes, Tumor-Infiltrating immunology, Lymphoma virology, Male, Middle Aged, Receptors, Cell Surface immunology, Retrospective Studies, T-Lymphocytes, Cytotoxic immunology, Young Adult, Central Nervous System Neoplasms immunology, Central Nervous System Neoplasms therapy, Lymphoma immunology, Lymphoma therapy, Tumor Microenvironment immunology
- Abstract
Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin lymphoma with an aggressive clinical course. To investigate the potential of immune-checkpoint therapy, we retrospectively studied the tumor microenvironment (TME) using high-plex immunohistochemistry in 22 PCNSL and compared to 7 secondary CNS lymphomas (SCNSL) and 7 "other" CNSL lymphomas with the presence of the Epstein-Barr virus and/or compromised immunity. The TME in PCNSL was predominantly composed of CD8+ cytotoxic T cells and CD163+ phagocytes. Despite molecular differences between PCNSL and SCNSL, the cellular composition and the functional spectrum of cytotoxic T cells were similar. But cytotoxic T cell activation was significantly influenced by pre-biopsy corticosteroids intake, tumor expression of PD-L1 and the presence of EBV. The presence of low numbers of CD8+ T cells and geographic-type necrosis each predicted inferior outcome in PCNSL. Both M1-like (CD68 + CD163
low ) and M2-like (CD68 + CD163high ) phagocytes were identified, and an increased ratio of M1-like/M2-like phagocytes was associated with a better survival. PD-L1 was expressed in lymphoma cells in 28% of cases, while PD1 was expressed in only 0.4% of all CD8+ T cells. TIM-3, a marker for T cell exhaustion, was significantly more expressed in CD8pos PD-1pos T cells compared to CD8pos PD-1neg T cells, and a similar increased expression was observed in M2-like pro-tumoral phagocytes. In conclusion, the clinical impact of TME composition supports the use of immune-checkpoint therapies in PCNSL. Based on observed differences in immune-checkpoint expression, combinations that boost cytotoxic T cell activation (by blocking TIM-3 or TGFBR1) prior to the administration of PD-L1 inhibition could be of interest.- Published
- 2020
- Full Text
- View/download PDF
86. Gastric Tumoral Melanosis: a Rare Manifestation of Successfully Treated Malignant Melanoma.
- Author
-
Bronswijk M, Sagaert X, and Bechter OE
- Subjects
- Humans, Melanoma diagnosis, Melanosis diagnosis, Skin Neoplasms
- Published
- 2020
- Full Text
- View/download PDF
87. An Integrated Gene Expression Landscape Profiling Approach to Identify Lung Tumor Endothelial Cell Heterogeneity and Angiogenic Candidates.
- Author
-
Goveia J, Rohlenova K, Taverna F, Treps L, Conradi LC, Pircher A, Geldhof V, de Rooij LPMH, Kalucka J, Sokol L, García-Caballero M, Zheng Y, Qian J, Teuwen LA, Khan S, Boeckx B, Wauters E, Decaluwé H, De Leyn P, Vansteenkiste J, Weynand B, Sagaert X, Verbeken E, Wolthuis A, Topal B, Everaerts W, Bohnenberger H, Emmert A, Panovska D, De Smet F, Staal FJT, Mclaughlin RJ, Impens F, Lagani V, Vinckier S, Mazzone M, Schoonjans L, Dewerchin M, Eelen G, Karakach TK, Yang H, Wang J, Bolund L, Lin L, Thienpont B, Li X, Lambrechts D, Luo Y, and Carmeliet P
- Published
- 2020
- Full Text
- View/download PDF
88. Interobserver, intraobserver, and interlaboratory variability in reporting pT4a colon cancer.
- Author
-
Klaver CEL, Bulkmans N, Drillenburg P, Grabsch HI, van Grieken NCT, Karrenbeld A, Koens L, van Lijnschoten I, Meijer J, Nagtegaal ID, Sagaert X, Seldenrijk K, van Velthuysen MF, Bruggink AH, Tanis PJ, and Snaebjornsson P
- Subjects
- Adenocarcinoma diagnosis, Colonic Neoplasms diagnosis, Humans, Neoplasm Invasiveness pathology, Observer Variation, Prognosis, Retrospective Studies, Adenocarcinoma pathology, Colonic Neoplasms pathology, Lymphatic Metastasis pathology, Peritoneum pathology
- Abstract
Clinical significance of the pT4 category in colon cancer is increasing with several therapeutic implications. The aim of this study was to evaluate variability in diagnosing pT4a colon cancer. Twelve pathologists classified 66 preselected scanned Hematoxylin/Eosin-stained slides with tumor cells at a distance of 25-1500 μm (n = 22), 0-25 μm (n = 22), or on (n = 22) the peritoneal surface. Inter- and intraobserver variability were calculated using Kappa statistics. For interlaboratory variability, pathology reports of pT3 and pT4a colon cancer were extracted from the Dutch Pathology Registry between 2012 and 2015. The proportion of pT4a (pT4a/(pT3+pT4a)) was compared between 33 laboratories. Potential risk of understaging was assessed by determining the average number of blocks taken from pT3 and pT4a N0-2M0 tumors with metachronous peritoneal metastasis. Interobserver variability among 12 pathologists was 0.50 (95%CI 0.41-0.60; moderate agreement). Intraobserver variability (8 pathologists) was 0.71 (substantial agreement). A total of 7745 reports with pT3 or pT4aN0-2M0 colon cancer from 33 laboratories were included for interlaboratory analysis. Median percentage of pT4a was 15.5% (range 3.2-24.6%). After adjustment for case mix, 8 labs diagnosed pT4a significantly less or more frequently than the median lab. Metachronous peritoneal metastases were histologically verified in 170 of 6629 pT3 and in 129 of 1116 pT4a tumors, with a mean number of blocks of 4.03(SD 1.51) and 4.78 (SD 1.76) taken from the primary tumors, respectively (p < 0.001). A substantial variability in diagnosing pT4a colon cancer exists, both at pathologist and laboratory level. Diagnosis of pT4a stage appears to be challenging and there is a need for standardizing assessment of this pathological entity.
- Published
- 2020
- Full Text
- View/download PDF
89. Guidelines for an optimal management of a malignant colorectal polyp. What is essential in a pathology report ?
- Author
-
Dano H, Baldin P, Demetter P, Driessen A, Hoorens A, Sagaert X, Van Huysse J, Verset L, and Jouret-Mourin A
- Subjects
- Colonoscopy, Colorectal Neoplasms, Humans, Practice Guidelines as Topic, Risk Factors, Colonic Polyps
- Abstract
Colorectal cancer (CRC) has become the most common malignancy in our country. Routine screening colonoscopy is on the rise. With the recent advances in endoscopic treatment, many T1 colorectal carcinomas are now found and their percentage amenable to endoscopic resection has increased. Endoscopists and pathologists dealing with the steadily increasing number of excised colorectal polyps have to collaborate closely to optimize patient care. Therapeutic management of patients after endoscopic resection is based on precise histological criteria that determine the risk of metastasis and the need for complementary surgery. This paper summarizes the procedures for the macroscopic management of endoscopic excisions and presents the identified risk factors which should be included in a standardized pathology report., Competing Interests: The authors declare that they have no conflict of interest, (© Acta Gastro-Enterologica Belgica.)
- Published
- 2020
90. Rapid clinical mutational testing of KRAS , BRAF and EGFR : a prospective comparative analysis of the Idylla technique with high-throughput next-generation sequencing.
- Author
-
Van Haele M, Vander Borght S, Ceulemans A, Wieërs M, Metsu S, Sagaert X, and Weynand B
- Subjects
- Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, ErbB Receptors genetics, Humans, Lung Neoplasms genetics, Lung Neoplasms pathology, Melanoma genetics, Melanoma secondary, Neoplasms pathology, Predictive Value of Tests, Prospective Studies, Reproducibility of Results, Skin Neoplasms genetics, Skin Neoplasms pathology, Workflow, Biomarkers, Tumor genetics, DNA Mutational Analysis methods, High-Throughput Nucleotide Sequencing, Mutation, Neoplasms genetics, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins p21(ras) genetics
- Abstract
Aims: Precision medicine therapy is remodelling the diagnostic landscape of cancer. The success of these new therapies is often based on the presence or absence of a specific mutation in a tumour. The Idylla platform is designed to determine the mutational status of a tumour as quickly and accurately as possible, as a rapid, accurate diagnosis is of the utmost importance for the treatment of patients. This is the first complete prospective study to investigate the robustness of the Idylla platform for EGFR , KRAS and BRAF mutations in non-small cell lung cancer, metastatic colorectal cancer and metastatic melanoma, respectively., Methods: We compared prospectively the Idylla platform with the results we obtained from parallel high-throughput next-generation sequencing, which is the current gold standard for mutational testing. Furthermore, we evaluated the benefits and disadvantages of the Idylla platform in clinical practice. Additionally, we reviewed all the published Idylla performance articles., Results: There was an overall agreement of 100%, 94% and 94% between the next-generation panel and the Idylla BRAF , KRAS and EGFR mutation test. Two interesting discordant findings among 48 cases were observed and will be discussed together with the advantages and shortcoming of both techniques., Conclusion: Our observations demonstrate that the Idylla cartridge for the EGFR , KRAS and BRAF mutations is highly accurate, rapid and has a limited hands-on time compared with next-generation sequencing., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2020
- Full Text
- View/download PDF
91. Delayed Bleeding of the Transplant Duodenum After Simultaneous Kidney-pancreas Transplantation: Case Series.
- Author
-
Van Mellaert A, Gillard P, Jochmans I, Demedts I, Sagaert X, Naesens M, Monbaliu D, Kuypers D, Pirenne J, and Sprangers B
- Subjects
- Aged, Allografts transplantation, Anastomosis, Surgical adverse effects, Diabetes Mellitus, Type 1 complications, Duodenal Diseases etiology, Duodenum transplantation, Female, Graft Survival, Humans, Kidney Failure, Chronic etiology, Kidney Transplantation methods, Male, Middle Aged, Pancreas Transplantation methods, Postoperative Hemorrhage etiology, Diabetes Mellitus, Type 1 surgery, Duodenal Diseases epidemiology, Kidney Failure, Chronic surgery, Kidney Transplantation adverse effects, Pancreas Transplantation adverse effects, Postoperative Hemorrhage epidemiology
- Abstract
Background: In simultaneous pancreas-kidney (SPK) transplant recipients, the majority of complications described in the literature, are early postoperative complications. However, there is growing attention for late complications associated with SPK transplantation., Methods: In this case series, we present 3 cases, 2 enterically and 1 bladder-derived SPK transplant patients, with anastomotic hemorrhage of the donor duodenum as a very late complication, >10 years after transplantation (11, 22, and 18 y later, respectively)., Results: In our center, 122 SPK transplantations have been performed between January 1992 and June 2018. The 3 cases reported here are the only patients in our cohort presenting with delayed anastomotic hemorrhage of the donor duodenum (2.5%). In the first 2 patients, reintervention with reconstruction of the anastomosis was performed. A congestive and friable mucosa was seen, and the resection specimen showed enlarged and congestive submucosal veins in both patients. There was no recurrence of bleeding after reintervention. In the third patient, enteric derivation was not possible because of the extremely fragile intestinal tissue perioperatively, and a conservative approach was taken. As possible precipitating factors are concerned, all 3 of our patients were taking low-dose aspirin and/or clopidogrel as secondary cardiovascular prevention., Conclusions: Bleeding of the transplanted donor duodenum can present as a late complication, several years after SPK transplantation. The development of enlarged, congestive submucosal veins could play a role in these late bleedings, and antiplatelet therapy could be a precipitating factor. Further research is necessary to investigate the pathophysiology, the prevalence, optimal treatment, and the consequent influence on mortality, morbidity, and graft loss after SPK transplantation.
- Published
- 2020
- Full Text
- View/download PDF
92. PD-1/PD-L1 immune checkpoint and p53 loss facilitate tumor progression in activated B-cell diffuse large B-cell lymphomas.
- Author
-
Pascual M, Mena-Varas M, Robles EF, Garcia-Barchino MJ, Panizo C, Hervas-Stubbs S, Alignani D, Sagardoy A, Martinez-Ferrandis JI, Bunting KL, Meier S, Sagaert X, Bagnara D, Guruceaga E, Blanco O, Celay J, Martínez-Baztan A, Casares N, Lasarte JJ, MacCarthy T, Melnick A, Martinez-Climent JA, and Roa S
- Subjects
- Animals, B-Lymphocytes pathology, B7-H1 Antigen genetics, Female, Humans, Immunotherapy, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse pathology, Lymphoma, Large B-Cell, Diffuse therapy, Male, Mice, Mice, Transgenic, Programmed Cell Death 1 Receptor genetics, T-Lymphocytes immunology, T-Lymphocytes pathology, Tumor Suppressor Protein p53 genetics, B-Lymphocytes immunology, B7-H1 Antigen immunology, Gene Expression Regulation, Neoplastic, Lymphocyte Activation, Lymphoma, Large B-Cell, Diffuse immunology, Programmed Cell Death 1 Receptor immunology, Tumor Escape, Tumor Suppressor Protein p53 immunology
- Abstract
Refractory or relapsed diffuse large B-cell lymphoma (DLBCL) often associates with the activated B-cell-like (ABC) subtype and genetic alterations that drive constitutive NF-κB activation and impair B-cell terminal differentiation. Here, we show that DNA damage response by p53 is a central mechanism suppressing the pathogenic cooperation of IKK2ca-enforced canonical NF-κB and impaired differentiation resulting from Blimp1 loss in ABC-DLBCL lymphomagenesis. We provide evidences that the interplay between these genetic alterations and the tumor microenvironment select for additional molecular addictions that promote lymphoma progression, including aberrant coexpression of FOXP1 and the B-cell mutagenic enzyme activation-induced deaminase, and immune evasion through major histocompatibility complex class II downregulation, PD-L1 upregulation, and T-cell exhaustion. Consistently, PD-1 blockade cooperated with anti-CD20-mediated B-cell cytotoxicity, promoting extended T-cell reactivation and antitumor specificity that improved long-term overall survival in mice. Our data support a pathogenic cooperation among NF-κB-driven prosurvival, genetic instability, and immune evasion mechanisms in DLBCL and provide preclinical proof of concept for including PD-1/PD-L1 blockade in combinatorial immunotherapy for ABC-DLBCL., (© 2019 by The American Society of Hematology.)
- Published
- 2019
- Full Text
- View/download PDF
93. Solid Tumor-Induced Immune Regulation Alters the GvHD/GvT Paradigm after Allogenic Bone Marrow Transplantation.
- Author
-
Dang N, Lin Y, Rutgeerts O, Sagaert X, Billiau AD, Waer M, and Sprangers B
- Subjects
- Animals, Female, Melanoma, Experimental immunology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Models, Animal, T-Lymphocytes, Regulatory immunology, Transplantation, Homologous, Tumor Microenvironment, Bone Marrow Transplantation, Graft vs Host Disease immunology, Melanoma, Experimental therapy
- Abstract
Growth of solid tumors is often associated with the development of an immunosuppressive tumor microenvironment (TME). It has been suggested that the influence of the TME may extend beyond the local tumor and results in systemic immunosuppression. Here, we utilize two murine cancer models to explore the influence of solid tumors on the occurrence of alloreactivity-driven GvHD and graft-versus-solid tumor (GvT) effects following MHC-mismatched allogeneic bone marrow transplantation (allo-BMT). Melanoma- or colon carcinoma-bearing C57BL/6 mice did not develop GvHD after BMT even when the bone marrow inoculum was supplemented with donor-type splenocytes. This protection against GvHD required the presence of tumors because its resection prior to allo-BMT promptly resulted in development of GvHD. In addition, tumor-bearing mice given T-cell-depleted allo-BMT (allo-TCD-BMT) failed to develop GvHD and also showed significantly stronger GvT effects than mice given allo-BMT. The GvT effects in allo-TCD-BMT recipients were associated with profound changes in tumor-infiltrating cells compared with that in allo-BMT recipients, with significantly reduced donor-derived regulatory T cells (Treg), increased cytotoxic effector (IFNγ
hi ) CD8 T cells, and increased M1 macrophages (iNOShi , arginaselo , and IL10lo ); the use of macrophage-depleted bone marrow abrogated the GvT effects. Collectively, these results indicate that the presence of M1 macrophages may disrupt the generation of donor-type Treg cells so that the immunomodulatory effect of the TME can affect systemic immunity. SIGNIFICANCE: These findings show that cells such as T cells or macrophages in the bone marrow inoculum may interfere with the systemic and local immune reactivity against tumors., (©2019 American Association for Cancer Research.)- Published
- 2019
- Full Text
- View/download PDF
94. MALT Lymphoma as a Model of Chronic Inflammation-Induced Gastric Tumor Development.
- Author
-
Marcelis L, Tousseyn T, and Sagaert X
- Subjects
- Helicobacter Infections microbiology, Helicobacter Infections pathology, Helicobacter pylori pathogenicity, Humans, Inflammation drug therapy, Inflammation immunology, Lymphoma, B-Cell, Marginal Zone drug therapy, Lymphoma, B-Cell, Marginal Zone immunology, Lymphoma, B-Cell, Marginal Zone microbiology, NF-kappa B metabolism, Stomach Neoplasms drug therapy, Stomach Neoplasms microbiology, Inflammation pathology, Lymphoma, B-Cell, Marginal Zone pathology, Stomach Neoplasms pathology
- Abstract
Mucosa-associated lymphoid tissue (MALT) lymphoma, or extranodal marginal zone lymphoma of MALT, is an indolent B-cell non-Hodgkin lymphoma linked with preexisting chronic inflammation. The stomach is the most commonly affected organ and the MALT lymphoma pathogenesis is clearly associated with Helicobacter pylori gastroduodenitis. Inflammation induces the lymphoid infiltrates in extranodal sites, where the lymphoma then subsequently develops. Genetic aberrations arise through the release of reactive oxygen species (ROS), H. pylori-induced endonucleases, and other effects. The involvement of nuclear factor kappa B (NF-κB) pathway activation, a critical regulator of pro-inflammatory responses, further highlights the role of inflammation in gastric MALT lymphoma. The NF-κB pathway regulates key elements of normal lymphocyte function, including the transcription of proliferation-promoting and anti-apoptotic genes. Aberrant constitutive activation of NF-κB signaling can lead to autoimmunity and malignancy. NF-κB pathway activation can happen through both the canonical and non-canonical pathways and can be caused by multiple genetic aberrations such as t(11;18)(q12;q21), t(1;14)(p22;q32), and t(14;18)(q32;q21) translocations, chronic inflammation and even directly by H. pylori-associated mechanisms. Gastric MALT lymphoma is considered one of the best models of how inflammation initiates genetic events that lead to oncogenesis, determines tumor biology, dictates clinical behavior and leads to viable therapeutic targets. The purpose of this review is to present gastric MALT lymphoma as an outstanding example of the close pathogenetic link between chronic inflammation and tumor development and to describe how this information can be integrated into daily clinical practice.
- Published
- 2019
- Full Text
- View/download PDF
95. Quiescent Endothelial Cells Upregulate Fatty Acid β-Oxidation for Vasculoprotection via Redox Homeostasis.
- Author
-
Kalucka J, Bierhansl L, Conchinha NV, Missiaen R, Elia I, Brüning U, Scheinok S, Treps L, Cantelmo AR, Dubois C, de Zeeuw P, Goveia J, Zecchin A, Taverna F, Morales-Rodriguez F, Brajic A, Conradi LC, Schoors S, Harjes U, Vriens K, Pilz GA, Chen R, Cubbon R, Thienpont B, Cruys B, Wong BW, Ghesquière B, Dewerchin M, De Bock K, Sagaert X, Jessberger S, Jones EAV, Gallez B, Lambrechts D, Mazzone M, Eelen G, Li X, Fendt SM, and Carmeliet P
- Subjects
- Animals, Cell Proliferation, HEK293 Cells, Homeostasis, Humans, Mice, Mice, Inbred C57BL, Oxidation-Reduction, Oxidative Stress, Carnitine O-Palmitoyltransferase metabolism, Energy Metabolism, Fatty Acids metabolism, Human Umbilical Vein Endothelial Cells metabolism, NADP metabolism, Receptor, Notch1 metabolism
- Abstract
Little is known about the metabolism of quiescent endothelial cells (QECs). Nonetheless, when dysfunctional, QECs contribute to multiple diseases. Previously, we demonstrated that proliferating endothelial cells (PECs) use fatty acid β-oxidation (FAO) for de novo dNTP synthesis. We report now that QECs are not hypometabolic, but upregulate FAO >3-fold higher than PECs, not to support biomass or energy production but to sustain the tricarboxylic acid cycle for redox homeostasis through NADPH regeneration. Hence, endothelial loss of FAO-controlling CPT1A in CPT1A
ΔEC mice promotes EC dysfunction (leukocyte infiltration, barrier disruption) by increasing endothelial oxidative stress, rendering CPT1AΔEC mice more susceptible to LPS and inflammatory bowel disease. Mechanistically, Notch1 orchestrates the use of FAO for redox balance in QECs. Supplementation of acetate (metabolized to acetyl-coenzyme A) restores endothelial quiescence and counters oxidative stress-mediated EC dysfunction in CPT1AΔEC mice, offering therapeutic opportunities. Thus, QECs use FAO for vasculoprotection against oxidative stress-prone exposure., (Copyright © 2018 Elsevier Inc. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF
96. Other immunomodulatory agent-related lymphoproliferative diseases: a single-center series of 72 biopsy-confirmed cases.
- Author
-
Marcelis L, Berghen C, De Zutter A, Biesemans P, Vandenberghe P, Verhoef G, Gheysens O, Sagaert X, Dierickx D, and Tousseyn T
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Female, Humans, Lymphoproliferative Disorders chemically induced, Lymphoproliferative Disorders mortality, Male, Middle Aged, Survival Rate, Young Adult, Immunosuppressive Agents adverse effects, Lymphoproliferative Disorders pathology
- Abstract
Ongoing development of new drugs, as well as novel indications in the treatment of autoimmune diseases leads to the increasing use of immunomodulatory and immunosuppressive drugs. Immunomodulatory agent-related lymphoproliferative disorders are a known and potentially life threatening complication of chronic administration of these drugs, but are less well characterized compared with post-transplant lymphoproliferative disorders. The heterogeneous drug targets, various underlying disease indications, different drug combinations used and relatively low incidence render data collection and interpretation difficult. In this retrospective paper, we describe the clinicopathological characteristics of a larger single-center series of 72 immunomodulatory agent-related lymphoproliferative disorder cases. We divided the cases according to the therapy, administered in the year preceding diagnosis of a lymphoproliferative disorder, in an immunosuppressive drug, an immunomodulatory drug and a combination of immunosuppressive and immunomodulatory drugs group. We observed differences in "time to lymphoproliferative disorder development" with a shorter time for all the immunomodulatory drug-related cases combined (immunomodulatory and immunomodulatory + immunosuppressive = immunomodulatory-all) vs immunosuppressive-only (p = 0.0031). The proportion of malignant cases in patients receiving immunomodulatory therapy was, however, also significantly lower when compared with the immunosuppressive treated cases (43 vs 88%; p = 0.0184). The immunomodulatory/suppressive agent-related lymphoproliferative disorders were less often associated with the Epstein-Barr virus (EBV) (31 vs 66%; p = 1.829e-05) and the lymphoproliferative disorders incidence in the first year after immunomodulatory/immunosuppressive therapy initiation was lower (18 vs 41%; p = 0.04151)-compared with a published series of 140 post-transplant lymphoproliferative disorder cases from the same center. However, a similar histopathological spectrum from nondestructive, to polymorphic and monomorphic lesions as in post-transplant lymphoproliferative disorders is observed. With increasing use of immunosuppressive and especially immunomodulatory therapy, a higher incidence of immunomodulatory/suppressive agent-related lymphoproliferative disorders is to be expected. Life-long awareness for development of immunomodulatory/suppressive agent-related lymphoproliferative disorders with clinical follow-up and timely biopsies of suspicious lesions is required since these lymphoproliferative disorders arise both early after therapy initiation and many years later. Histopathological confirmation and correct classification is necessary to guide therapy and EBV ISH should be a part of routine pathological diagnostics.
- Published
- 2018
- Full Text
- View/download PDF
97. Correction to: Secondary B-cell lymphoma associated with the Epstein-Barr virus in chronic lymphocytic leukemia patients.
- Author
-
Morscio J, Bittoun E, Volders N, Lurquin E, Wlodarska I, Gheysens O, Vandenberghe P, Verhoef G, Demaerel P, Dierickx D, Sagaert X, Janssens A, and Tousseyn T
- Abstract
[This corrects the article DOI: 10.1007/s12308-016-0273-8.].
- Published
- 2018
- Full Text
- View/download PDF
98. Richter transformation driven by Epstein-Barr virus reactivation during therapy-related immunosuppression in chronic lymphocytic leukaemia.
- Author
-
García-Barchino MJ, Sarasquete ME, Panizo C, Morscio J, Martinez A, Alcoceba M, Fresquet V, Gonzalez-Farre B, Paiva B, Young KH, Robles EF, Roa S, Celay J, Larrayoz M, Rossi D, Gaidano G, Montes-Moreno S, Piris MA, Balanzategui A, Jimenez C, Rodriguez I, Calasanz MJ, Larrayoz MJ, Segura V, Garcia-Muñoz R, Rabasa MP, Yi S, Li J, Zhang M, Xu-Monette ZY, Puig-Moron N, Orfao A, Böttcher S, Hernandez-Rivas JM, Miguel JS, Prosper F, Tousseyn T, Sagaert X, Gonzalez M, and Martinez-Climent JA
- Subjects
- Adult, Aged, B-Lymphocytes drug effects, B-Lymphocytes pathology, Cell Transformation, Neoplastic pathology, Epstein-Barr Virus Infections drug therapy, Epstein-Barr Virus Infections pathology, Female, Herpesvirus 4, Human genetics, Humans, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse genetics, Male, Middle Aged, Cell Transformation, Neoplastic drug effects, Herpesvirus 4, Human drug effects, Immunosuppressive Agents pharmacology, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
- Abstract
The increased risk of Richter transformation (RT) in patients with chronic lymphocytic leukaemia (CLL) due to Epstein-Barr virus (EBV) reactivation during immunosuppressive therapy with fludarabine other targeted agents remains controversial. Among 31 RT cases classified as diffuse large B-cell lymphoma (DLBCL), seven (23%) showed EBV expression. In contrast to EBV
- tumours, EBV+ DLBCLs derived predominantly from IGVH-hypermutated CLL, and they also showed CLL-unrelated IGVH sequences more frequently. Intriguingly, despite having different cellular origins, clonally related and unrelated EBV+ DLBCLs shared a previous history of immunosuppressive chemo-immunotherapy, a non-germinal centre DLBCL phenotype, EBV latency programme type II or III, and very short survival. These data suggested that EBV reactivation during therapy-related immunosuppression can transform either CLL cells or non-tumoural B lymphocytes into EBV+ DLBCL. To investigate this hypothesis, xenogeneic transplantation of blood cells from 31 patients with CLL and monoclonal B-cell lymphocytosis (MBL) was performed in Rag2-/- IL2γc-/- mice. Remarkably, the recipients' impaired immunosurveillance favoured the spontaneous outgrowth of EBV+ B-cell clones from 95% of CLL and 64% of MBL patients samples, but not from healthy donors. Eventually, these cells generated monoclonal tumours (mostly CLL-unrelated but also CLL-related), recapitulating the principal features of EBV+ DLBCL in patients. Accordingly, clonally related and unrelated EBV+ DLBCL xenografts showed indistinguishable cellular, virological and molecular features, and synergistically responded to combined inhibition of EBV replication with ganciclovir and B-cell receptor signalling with ibrutinib in vivo. Our study underscores the risk of RT driven by EBV in CLL patients receiving immunosuppressive therapies, and provides the scientific rationale for testing ganciclovir and ibrutinib in EBV+ DLBCL. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)- Published
- 2018
- Full Text
- View/download PDF
99. ypT0N+: the unusual patient with pathological complete tumor response but with residual lymph node disease after neoadjuvant chemoradiation for esophageal cancer, what's up?
- Author
-
Depypere LP, Vervloet G, Lerut T, Moons J, De Hertogh G, Sagaert X, Coosemans W, Van Veer H, and Nafteux PR
- Abstract
Background: Little is known about the prognostic significance of residual nodal disease in otherwise complete pathologic responders (ypT0N+) after neoadjuvant chemoradiation (nCRT) for esophageal cancer (EC). The purpose is to analyze the long-term outcomes of EC patients with ypT0N+ following nCRT and esophagectomy., Methods: From a single institution database, 466 consecutive EC patients undergoing esophagectomy after nCRT were collected (1996-2016). ypT0N+ responders were compared to pathological complete responders (ypT0N0) and to pathological non-complete responders (ypT+N0 and ypT+N+)., Results: There were 149 ypT0N0, 31 ypT0N+, 141 ypT+N0 and 145 ypT+N+. Median overall survival (OS) was worse in ypT0N+ (21.7 months) and ypT+N+ (16.8 months) compared to ypT0N0 (55.2 months) and ypT+N0 (42.0 months). Stratification by histology revealed a significant difference in prevalence of ypT0: 62.5% in 184 squamous cell carcinomas (SCC) compared to 23.0% in 282 adenocarcinomas (ADC) (P<0.0001) but not in ypT0N+ (15% vs . 22% respectively, P=0.25). In ADC, locoregional recurrence in ypT0N+ (43%) was comparable to ypT+N+ (31%) and more common compared to ypT0N0 (7%) and ypT+N0 (10%), reflected in median OS rates of 20.6, 17.5, 53.0 and 36.6 months respectively. Median OS in ADC is significantly determined by number of positive lymph nodes, being 21.7 months for pN1 and 2.7 months for pN2/3 (P=0.005) in ypT0N+ and 33.7 months for pN1 and 16.2 months for pN2/3 (P=0.031) in ypT+N+. In SCC, locoregional recurrences were found in 17% of ypT0N+, 33% of ypT+N+, 11% of ypT0N0 and 22% in ypT+N0 and median OS was 26.6, 15.6, 55.2 and 43.8 months respectively. In SCC ypN+ number of affected lymph nodes showed no difference on OS., Conclusions: ypT0N+ in EC patients following nCRT has a poor prognosis and behaves similar to ypT+N+. However, stratification by histology shows that this is especially true in ADC but seems determined by the number of involved lymph nodes., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.
- Published
- 2018
- Full Text
- View/download PDF
100. Tumor Heterogeneity in Colorectal Cancer: What Do We Know So Far?
- Author
-
Sagaert X, Vanstapel A, and Verbeek S
- Subjects
- Colorectal Neoplasms diagnosis, Colorectal Neoplasms pathology, Humans, Mutation, Prognosis, Biomarkers, Tumor genetics, Colorectal Neoplasms genetics, Genetic Heterogeneity
- Abstract
Colorectal cancer is not one disease but rather a collection of neoplastic diseases. Due to heterogeneity in the disease biology, therapy response, and prognosis, extensive disease stratification is required. Therefore, TNM stage, microsatellite status, tumor grade, lymphovascular invasion, and other parameters are assessed in the pathology report to indicate the extent and prognosis of the disease. The mutation status of KRAS, BRAF, and NRAS is also investigated in a metastatic context to predict the response to anti-EGFR therapy. Recently, 4 distinct molecular subtypes of colorectal cancer have been described that have both prognostic and therapeutic relevance. In addition, characterization of the inflammatory infiltrate revealed major differences in the amount and location of inflammatory cells in distinct colorectal tumor types. Together, all of these parameters help to stratify patients into different therapeutic and prognostic subgroups. However, this stratification is not unambiguous since tumors often display intratumoral heterogeneity, whereby several subpopulations within one tumor show differences in morphology, inflammatory infiltrate, mutational status, or gene expression profile. This article gives an overview of all of the current known data with regard to tumor heterogeneity at both inter- and intratumoral levels., (© 2018 S. Karger AG, Basel.)
- Published
- 2018
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.