15 results on '"Willems, Stefan M."'
Search Results
2. Tumor Markers and Their Prognostic Value in Sinonasal ITAC/Non-ITAC.
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Veuger, Julius, Kuipers, Nona C., Willems, Stefan M., and Halmos, Gyorgy B.
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ADENOCARCINOMA ,BIOMARKERS ,ONLINE information services ,SURVIVAL ,SYSTEMATIC reviews ,ONCOGENES ,PARANASAL sinus cancer ,TREATMENT effectiveness ,DECISION making ,METHYLATION ,TUMOR markers ,MEDLINE ,VASCULAR endothelial growth factors ,RARE diseases - Abstract
Simple Summary: Prognostic markers play an important role in the risk assessment and treatment of cancers in general. The aim of this systematic review was to assess the potential prognostic markers for the rare sinonasal intestinal-type adenocarcinoma. The results from this paper may help specialists to better understand the risks of this disease and provide more insight into the prognosis. We found twenty-one biomarkers. Whilst some had a significant negative effect on prognosis, none had a positive effect. Furthermore, the biomarkers found were analyzed within the hallmarks of cancer to provide more information considering the carcinogenesis of this carcinoma. This could help in the better treatment of sinonasal intestinal-type adenocarcinoma and better patient outcomes. One of the rare tumor entities present in the nose and paranasal sinuses is sinonasal (non-) intestinal-type adenocarcinoma (ITAC/non-ITAC). Currently, surgery with postoperative radiotherapy is the cornerstone of the treatment of these tumors. Systemic treatment is usually applied in a palliative setting. The prognosis of these tumors is very diverse. Biomarkers that may have prognostic value in these rare malignancies could help clinicians in decision-making. A systematic search of the literature was performed using the PubMed database. All studies investigating the prognostic significance of biomarkers in paranasal sinus ITAC/non-ITAC were retrieved. The findings were categorized within the hallmarks of cancer, to gain an understanding of the functions of possible prognostic biomarkers in the development of ITAC/non-ITAC. There were twenty-one studies reporting on twenty-one possible biomarkers included in the review. The expression of Mucin antigen sialosyl-Tn, C-erbB-2 oncoprotein, TIMP3 methylation, TP53, VEGF, ANXA2, MUC1 and the mucinous histological subtype were found to have a significant negative effect on survival. None of the biomarkers were found to have a positive effect on prognosis. The hallmarks 'activating invasion and metastasis' and 'sustaining proliferative signaling' seem to play the largest role in sinonasal (non-)ITAC. It could be concluded that there are multiple biomarkers foreboding a negative prognosis for ITAC/non-ITAC patients. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Cathepsin K associates with lymph node metastasis and poor prognosis in oral squamous cell carcinoma
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Leusink, Frank K., Koudounarakis, Eleftherios, Frank, Michael H., Koole, Ronald, van Diest, Paul J., and Willems, Stefan M.
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- 2018
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4. Correlation and colocalization of HIF-1α and pimonidazole staining for hypoxia in laryngeal squamous cell carcinomas
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Swartz, Justin E., Smits, Hilde J.G., Philippens, Marielle E.P., de Bree, Remco, H.A.M. Kaanders, Johannes, Willems, Stefan M., Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
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EXPRESSION ,Cancer Research ,CLINICAL-RELEVANCE ,ADVANCED HEAD ,Image Processing ,Biomarkers/metabolism ,alpha Subunit/metabolism ,OXYGEN ,TUMOR HYPOXIA ,Laryngeal Neoplasms/pathology ,CHEMORADIATION ,Computer-Assisted ,Image Processing, Computer-Assisted ,Pathology ,Biomarkers, Tumor ,Tumor/metabolism ,Humans ,Hypoxia ,Laryngeal Neoplasms ,NECK ,Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ,Microscopy ,Staining and Labeling ,Squamous Cell Carcinoma of Head and Neck ,Reproducibility of Results ,PREDICTIVE-VALUE ,Hypoxia-Inducible Factor 1, alpha Subunit ,Prognosis ,Cell Hypoxia ,Oncology ,Head and Neck Neoplasms ,Nitroimidazoles ,Biomarkers, Tumor/metabolism ,INDUCIBLE FACTORS ,Hypoxia-Inducible Factor 1 ,Oral Surgery ,Biomarkers ,RADIOTHERAPY ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] - Abstract
Contains fulltext : 251419.pdf (Publisher’s version ) (Open Access) OBJECTIVE: Tumor hypoxia results in worse local control and patient survival. We performed a digital, single-cell-based analysis to compare two biomarkers for hypoxia (hypoxia-inducible factor 1-alpha [HIF-1alpha] and pimonidazole [PIMO]) and their effect on outcome in laryngeal cancer patients treated with accelerated radiotherapy with or without carbogen breathing and nicotinamide (AR versus ARCON). MATERIALS AND METHODS: Immunohistochemical staining was performed for HIF-1alpha and PIMO in consecutive sections of 44 laryngeal cancer patients randomized between AR and ARCON. HIF-1alpha expression and PIMO-binding were correlated using digital image analysis in QuPath. High-density areas for each biomarker were automatically annotated and staining overlap was analyzed. Kaplan-Meier survival analyses for local control, regional control and disease-free survival were performed to predict a response benefit of ARCON over AR alone for each biomarker. RESULTS: 106 Tissue fragments of 44 patients were analyzed. A weak, significant positive correlation was observed between HIF-1alpha and PIMO positivity on fragment level, but not on patient level. A moderate strength correlation (r = 0.705, p < 0.001) was observed between the number of high-density staining areas for both biomarkers. Staining overlap was poor. HIF-1alpha expression, PIMO-binding or a combination could not predict a response benefit of ARCON over AR. CONCLUSION: Digital image analysis to compare positive cell fractions and staining overlap between two hypoxia biomarkers using open-source software is feasible. Our results highlight that there are distinct differences between HIF-1alpha and PIMO as hypoxia biomarkers and therefore suggest co-existence of different forms of hypoxia within a single tumor.
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- 2022
5. Association of histological features with laryngeal squamous cell carcinoma recurrences: a population-based study of 1502 patients in the Netherlands
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Ruiter, Lilian N., van Dijk, Boukje A.C., Bruggink, Annette H., Doornaert, Patricia A.H., Philippens, Marielle E.P., de Bree, Remco, van Gils, Carla H., Willems, Stefan M., Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
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Cancer Research ,Histology ,Survival ,Squamous Cell Carcinoma of Head and Neck ,CHEMOTHERAPY ,Prognosis ,CANCER ,Laryngeal neoplasms ,TUMOR HYPOXIA ,Oncology ,TO-LYMPHOCYTE RATIO ,Head and Neck Neoplasms ,Recurrence ,Squamous cell carcinoma ,PROGNOSTIC-SIGNIFICANCE ,Genetics ,Carcinoma, Squamous Cell ,Pathology ,Humans ,Neoplasm Invasiveness ,HEAD ,Neoplasm Recurrence, Local ,Neoplasm Staging ,Netherlands ,Retrospective Studies - Abstract
Background Recurrences remain an important problem in laryngeal squamous cell carcinoma. Little has been described about histological characteristics of the primary laryngeal tumor that may be associated with recurrences. Identifying risk factors for recurrences might help in adapting treatment or follow-up. Using real-life population-based data, we aimed to identify histological features of the primary tumor associated with recurrences and overall survival. Material and methods Demographic, clinical and treatment information on all first primary invasive laryngeal tumors diagnosed in 2010–2014 (N = 3705) were extracted from the population-based nationwide Netherlands cancer registry (NCR) and linked to PALGA, the nationwide Dutch pathology registry, to obtain data on histological factors and recurrences. For a random 1502 patients histological information i.e., keratinization, perineural invasion (PNI+), vascular invasion (VI+), growth pattern, degree of differentiation, extracapsular spread (ECS+), cartilage- and bone invasion and extralaryngeal extension, was manually extracted from narrative pathology reports and analyzed for locoregional recurrence and overall survival using cox regression analysis. Results In total, 299 patients developed a locoregional recurrence and 555 patients died. Keratinization (HR = 0.96 (95%CI: 0.68–1.34) p = 0.79), two or three adverse characteristics (PNI+, VI+, non-cohesive growth) (HR = 1.38 (95% CI: 0.63–3.01) p = 0.42), and ECS+ (HR = 1.38 (95% CI: 0.48–4.02) p = 0.55) were not associated to recurrence. For death, also no significant association was found. Conclusion In this population-based real-life dataset on laryngeal carcinoma in the Netherlands, histological factors were not associated with locoregional recurrences or overall survival, but future studies should investigate the role of these features in treatment decisions.
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- 2022
6. HIF‐1a expression and differential effects on survival in patients with oral cavity, larynx, and oropharynx squamous cell carcinomas.
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Swartz, Justin E., Wegner, Inge, Noorlag, Rob, Kempen, Pauline M. W., Es, Robert J. J., Bree, Remco, and Willems, Stefan M. W.
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SQUAMOUS cell carcinoma ,PROGNOSIS ,LARYNX ,HYPOXIA-inducible factors ,OROPHARYNX - Abstract
Background: Hypoxia is a negative prognostic factor in head and neck squamous cell carcinomas. Under hypoxia, the hypoxia‐inducible factor (HIF)‐1a transcription factor is overexpressed. We investigated whether there were site differences in HIF‐1a expression and its effect on patient outcomes per subsite. Design/Method: A total of 941 patients with HNSCC in the squamous cell carcinoma of the oropharynx (OPSCC, n = 302), oral cavity (OSCC, n = 391), or larynx (LSCC, n = 248) were included. Expression of HIF‐1a in tissue samples was investigated using immunohistochemistry. Overall survival (OS), disease‐free survival (DFS), and locoregional control (LRC) were analyzed. Results: HIF‐1a expression was higher in OSCC than in LSCC and OPSCC. High HIF‐1a expression led to worse prognosis in OPSCC (OS P =.029, DFS P =.085) and LSCC (OS P =.041, DFS P =.011) and better in OSCC (OS P =.055, DFS P =.012). There was no association between HIF‐1a and LRC. Conclusions: High HIF‐1a expression is related to poor outcome in OPSCC and LSCC and better outcome in OSCC. [ABSTRACT FROM AUTHOR]
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- 2021
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7. A clinicopathological study and prognostic factor analysis of 177 salivary duct carcinoma patients from The Netherlands
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Boon, Eline, Bel, Miranda, van Boxtel, Wim, van der Graaf, Winette T. A., van Es, Robert J. J., Eerenstein, Simone E. J., Baatenburg de Jong, Robert J., van den Brekel, Michiel W. M., van der Velden, Lilly‐Ann, Witjes, Max J. H., Hoeben, Ann, Willems, Stefan M., Bloemena, Elisabeth, Smit, Laura A., Oosting, Sjoukje F., Jonker, Marianne A., Flucke, Uta E., van Herpen, Carla M. L., Guided Treatment in Optimal Selected Cancer Patients (GUTS), Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, MUMC+: MA Medische Oncologie (9), MKA AMC (OII, ACTA), MKA Vumc (OII, ACTA), and Otorhinolaryngology and Head and Neck Surgery
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Adult ,Male ,DATABASE ,Receptor, ErbB-2 ,receptor ,Receptor, ErbB-2/metabolism ,Receptors, Androgen/metabolism ,THERAPY ,survival ,Disease-Free Survival ,ErbB-2 ,Recurrence ,ErbB‐2 ,Journal Article ,FAILURE ,Humans ,Salivary Ducts ,Neoplasm Metastasis ,Carcinoma/pathology ,salivary duct carcinoma ,Aged ,Netherlands ,Aged, 80 and over ,OUTCOMES ,Carcinoma ,Palliative Care ,ANDROGEN RECEPTOR ,Salivary Ducts/pathology ,Chemoradiotherapy, Adjuvant ,Middle Aged ,Prognosis ,Salivary Gland Neoplasms ,Survival Rate ,androgen receptors ,Receptors, Androgen ,Lymphatic Metastasis ,immunohistochemistry ,Female ,in situ hybridization ,fluorescence ,Factor Analysis, Statistical ,Salivary Gland Neoplasms/pathology ,Cancer Epidemiology - Abstract
Salivary duct carcinoma (SDC) is a subtype of salivary gland cancer with a dismal prognosis and a need for better prognostication and novel treatments. The aim of this national cohort study was to investigate clinical outcome, prognostic factors, androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) expression. SDC patients diagnosed between 1990 and 2014 were identified by the Nationwide Network and Registry of Histo‐ and Cytopathology in the Netherlands (PALGA). Subsequently, medical records were evaluated and pathological diagnoses reviewed. Data were analyzed for overall survival (OS), disease‐free survival (DFS), distant metastasis‐free survival (DMFS) and prognostic factors. AR was evaluated by immunohistochemistry (IHC), HER2 by IHC and fluorescent in‐situ hybridization. A total of 177 patients were included. The median age was 65 years, 75% were male. At diagnosis, 68% presented with lymph node metastases and 6% with distant metastases. Median OS, DFS and DMFS were 51, 23 and 26 months, respectively. In patients presenting without distant metastases, the absolute number of positive lymph nodes was associated with poor OS and DMFS in a multivariable analysis. AR and HER2 were positive in 161/168 (96%) and 44/153 (29%) tumors, respectively, and were not prognostic factors. SDC has a dismal prognosis with primary lymph node involvement in the majority of patients. The absolute number of lymph node metastases was found to be the only prognostic factor for DMFS and OS. AR expression and—to a lesser extent—HER2 expression hold promise for systemic treatment in the metastatic and eventually adjuvant setting., What's new? Salivary duct carcinoma (SDC) is a rare and often fatal malignancy. Little is known about associations between its pathological features and clinical outcome. In this study, clinicopathological factors were analyzed for 177 patients diagnosed with SDC in The Netherlands between 1990 and 2014. The data show that median overall survival (OS) and distant metastasis‐free survival (DMFS) were 51 and 26 months, respectively. At diagnosis, 68% of patients presented with lymph node metastases. Lymph node positivity was associated with poor OS and poor DMFS. The absolute number of metastatic lymph nodes was the only significant prognostic factor for survival in a multivariate analysis. Androgen receptor and human epidermal growth factor 2 (HER2) were positive in 96% and 29%, respectively and were not a prognostic factor.
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- 2018
8. HPV-positive oropharyngeal squamous cell carcinoma is associated with TIMP3 and CADM1 promoter hypermethylation
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van Kempen, Pauline M W, van Bockel, Liselotte, Braunius, Weibel W, Moelans, Cathy B, van Olst, Marina, de Jong, Rick, Stegeman, Inge, van Diest, Paul J, Grolman, Wilko, and Willems, Stefan M
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Adult ,Male ,HPV ,TIMP3 ,Immunoglobulins ,CHFR ,oropharynx squamous cell carcinoma ,Risk Factors ,Humans ,Promoter Regions, Genetic ,Papillomaviridae ,Cancer Biology ,Original Research ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Tissue Inhibitor of Metalloproteinase-3 ,Papillomavirus Infections ,Cell Adhesion Molecule-1 ,virus diseases ,DNA Methylation ,Middle Aged ,Prognosis ,female genital diseases and pregnancy complications ,Tumor Burden ,hypermethylation ,Oropharyngeal Neoplasms ,Carcinoma, Squamous Cell ,Female ,CADM1 ,Cell Adhesion Molecules - Abstract
Oropharyngeal squamous cell carcinoma (OPSCC) is associated with human papillomavirus (HPV) in a proportion of tumors. HPV-positive OPSCC is considered a distinct molecular entity with a prognostic advantage compared to HPV-negative cases. Silencing of cancer-related genes by DNA promoter hypermethylation may play an important role in the development of OPSCC. Hence, we examined promoter methylation status in 24 common tumor suppressor genes in a group of 200 OPSCCs to determine differentially methylated genes in HPV-positive versus HPV-negative primary OPSCC. Methylation status was correlated with HPV status, clinical features, and patient survival using multivariate methods. Additionally, methylation status of 16 cervical squamous cell carcinomas (SCC) was compared with HPV-positive OPSCC. Using methylation-specific probe amplification, HPV-positive OPSCC showed a significantly higher cumulative methylation index (CMI) compared to HPV-negative OPSCC (P=0.008). For the genes CDH13, DAPK1, and RARB, both HPV-positive and HPV-negative OPSCC showed promoter hypermethylation in at least 20% of the tumors. HPV status was found to be an independent predictor of promoter hypermethylation of CADM1 (P < 0.001), CHFR (P = 0.027), and TIMP3 (P < 0.001). CADM1 and CHFR showed similar methylation patterns in OPSCC and cervical SCC, but TIMP3 showed no methylation in cervical SCC in contrast to OPSCC. Methylation status of neither individual gene nor CMI was associated with survival. These results suggest that HPV-positive tumors are to a greater extent driven by promotor hypermethylation in these tumor suppressor genes. Especially CADM1 and TIMP3 are significantly more frequently hypermethylated in HPV-positive OPSCC and CHFR in HPV-negative tumors.
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- 2014
9. Prognostic value of the nodal yield in head and neck squamous cell carcinoma: A systematic review.
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Kort, Willem W. B., Maas, Sybren L. N., Van Es, Robert J. J., and Willems, Stefan M.
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SQUAMOUS cell carcinoma ,META-analysis ,ONCOLOGIC surgery ,LYMPHADENECTOMY ,LYMPH nodes - Abstract
Objective: Literature analysis on the prognostic factor of the nodal yield (NY) in neck dissections (NDs), which in general surgical oncology is a strong prognosticator and quality‐of‐care marker. Methods: We performed a systematic review of all PubMed and Embase publications until June 30, 2018 screening for data on NY as prognosticator and overall survival (OS) as outcome in patients with head and neck squamous cell carcinoma (HNSCC). Risk for bias was asserted by application of the Quality In Prognosis Studies tool. Results: Of the 823 screened publications, 15 were included in this analysis. Five out of seven that compared NY ≥18 vs <18 as prognosticator, showed significantly improved survival if NY ≥18. Six studies used other cutoffs and three reported improved survival with each additionally harvested lymph node. Conclusion: Increased NY in ND specimen for HNSCC, most commonly described as ≥18 lymph nodes, is associated with improved OS and could be used as a prognosticator and quality‐of‐care marker. [ABSTRACT FROM AUTHOR]
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- 2019
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10. Prognostic role of tumor infiltrating lymphocytes in EBV positive and EBV negative nasopharyngeal carcinoma.
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Ooft, Marc L., Willems, Stefan M., van Ipenburg, Jolique A., Koljenović, Senada, Braunius, Weibel W., and Zuur, Charlotte I.
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LYMPHOCYTES , *EPSTEIN-Barr virus diseases , *CANCER immunotherapy , *PROGRESSION-free survival , *APOPTOSIS , *CD antigens , *DISEASE risk factors , *DISEASES , *CANCER , *EPSTEIN-Barr virus , *PROGNOSIS ,NASOPHARYNX tumors - Abstract
Objectives: Tumor infiltrating lymphocytes (TILs) correlate with both better and worse prognosis in solid tumors. As therapeutic modalities for nasopharyngeal carcinoma (NPC) are limited, immunotherapy could be a potential alternative. Up till now there is limited prognostic data on the role of TILs in NPC, so we assessed the prognostic role of TILs in Epstein-Barr-virus (EBV) positive and negative NPC.Methods: Tissue of 92 NPCs was assessed for CD3, CD4, CD8, PD1 and PDL1 expression in the tumor's micro-environment. Correlations between clinicopathological characteristics was assessed using the Pearson X2 test, Fisher's exact test and ANOVA. Survival was analyzed with the Kaplan-Meier method and Cox regression. Differences in CD3, CD4, CD8, PD1, PDL1 counts/(co)expression between EBV positive and negative NPCs were evaluated using the Mann-Whitney U test. Two-tailed P values below 0.05 were considered statistically significant.Results: EBV positive NPC contains significantly more CD3, CD4 and CD8 TILs than EBV negative NPC. In the whole NPC group, increased CD8 count is associated with better overall survival (OS) (HR 0.219 (95%CI 0.075-0.640)), but also in cases with PDL1 co-expression (HR 0.073 (95%CI 0.010-0.556)). In EBV positive NPC co-expression of CD8 and PDL1 showed better disease free survival (HR 0.407 (95%CI 0.195-0.850)) and OS (HR 0.170 (95%CI 0.037-0.787)).Conclusions: Although TILs are significantly different between EBV positive and negative NPCs, it is especially composition of the infiltrate which determines prognosis. Effects of PD1 and CD8 need more study, because these findings show much potential in using immunotherapeutic modalities in NPC treatment. [ABSTRACT FROM AUTHOR]- Published
- 2017
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11. Fibroblast Growth Factor Receptor Family Members as Prognostic Biomarkers in Head and Neck Squamous Cell Carcinoma: A Systematic Review.
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Ipenburg, Norbertus, Koole, Koos, Liem, K., Kempen, Pauline, Koole, Ron, Diest, Paul, Es, Robert, Willems, Stefan, Ipenburg, Norbertus A, Liem, K Seng, van Kempen, Pauline M W, van Diest, Paul J, van Es, Robert J J, and Willems, Stefan M
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CANCER treatment ,ANIMAL experimentation ,CELL receptors ,COMPARATIVE studies ,RESEARCH methodology ,MEDICAL cooperation ,HEAD tumors ,PROGNOSIS ,NECK tumors ,RESEARCH ,SQUAMOUS cell carcinoma ,SYSTEMATIC reviews ,EVALUATION research ,DIAGNOSIS ,TUMOR treatment - Abstract
Background: Since head and neck cancer is characterized by poor survival rates, there is a demand for novel therapeutic targets and prognostic biomarkers. An upcoming therapeutic target is the fibroblast growth factor receptor (FGFR) family. However, their prognostic role in head and neck cancer remains unclear.Objective: To systematically review current evidence on the prognostic value of FGFR family members in head and neck squamous cell carcinoma (HNSCC).Methods: A systematic search of PubMed, Embase, and the Cochrane Library was performed for publications up to 14 May 2014. Two reviewers screened all articles and included prognostic studies on the molecular biomarkers FGFR1-5 in any type of HNSCC. Relevant studies were assessed on risk of bias using the Quality in Prognostic Studies (QUIPS) tool. Data on FGFR aberrations and survival outcome were extracted from relevant studies. The prognostic value of FGFR aberrations was compared among studies.Results: The initial search yielded 1568 publications of which 12 fulfilled the inclusion criteria. Four studies reported FGFR1 gene amplification (9.3-17.4 %) and FGFR1 protein overexpression (11.8 %) in HNSCC. FGFR1 protein expression by cancer-associated fibroblasts correlated with poor survival outcome in one study (p < 0.01). Eight studies reported high rates of FGFR4 Gly388Arg polymorphisms (32.5-54.2 %) and FGFR4 protein overexpression (16-35 %), with varying correlations with survival. So far, no studies assessed the prognostic role of FGFR2, FGFR3, or FGFR5 in HNSCC.Limitations: Significant risk of bias has been identified among included studies. Therefore, cautious interpretation of the results is recommended.Conclusion: In conclusion, evidence was found for prognostic value of FGFR1 expression in cancer-associated fibroblasts in HNSCC. Prognostic evidence on the other FGFR family members in HNSCC is limited and conflicting. This emphasizes the need for future well-conducted prognostic studies. [ABSTRACT FROM AUTHOR]- Published
- 2016
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12. Promoter hypermethylation using 24-gene array in early head and neck cancer.
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Noorlag, Rob, van Kempen, Pauline M. W., Moelans, Cathy B., de Jong, Rick, Blok, Laura E. R., Koole, Ronald, Grolman, Wilko, van Diest, Paul J., van Es, Robert J. J., and Willems, Stefan M.
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- 2014
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13. Tumor-Infiltrating Lymphocytes in the Tumor Microenvironment of Laryngeal Squamous Cell Carcinoma: Systematic Review and Meta-Analysis †.
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Rodrigo, Juan P., Sánchez-Canteli, Mario, López, Fernando, Wolf, Gregory T., Hernández-Prera, Juan C., Williams, Michelle D., Willems, Stefan M., Franchi, Alessandro, Coca-Pelaz, Andrés, Ferlito, Alfio, Plzak, Jan, and Oriuchi, Noboru
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SQUAMOUS cell carcinoma ,TUMOR microenvironment ,OVERALL survival ,PROGNOSIS ,LYMPHOCYTES ,LARYNGEAL cancer - Abstract
The presence of tumor-infiltrating lymphocytes (TIL) in the tumor microenvironment has been demonstrated to be of prognostic value in various cancers. In this systematic review and meta-analysis, we investigated the prognostic value of TIL in laryngeal squamous cell carcinoma (LSCC). We performed a systematic search in PubMed for publications that investigated the prognostic value of TIL in LSCC. A meta-analysis was performed including all studies assessing the association between TIL counts in hematoxylin-eosin (HE)-stained sections, for CD8+ and/or CD3+/CD4+ TIL and overall survival (OS) or disease-free survival (DFS). The pooled meta-analysis showed a favorable prognostic role for stromal TIL in HE sections for OS (HR 0.57, 95% CI 0.36–0.91, p = 0.02), and for DFS (HR 0.56, 95% CI 0.34–0.94, p = 0.03). High CD8+ TIL were associated with a prolonged OS (HR 0.62, 95% CI 0.4–0.97, p = 0.04) and DFS (HR 0.73, 95% CI 0.34–0.94, p = 0.002). High CD3+/CD4+ TIL demonstrated improved OS (HR 0.32, 95% CI 0.16–0.9, p = 0.03) and DFS (HR 0.23, 95% CI 0.10–0.53, p = 0.0005). This meta-analysis confirmed the favorable prognostic significance of TIL in LSCC. High stromal TIL evaluated in HE sections and intra-tumoral and stromal CD3+, CD4+ and/or CD8+ TIL might predict a better clinical outcome. [ABSTRACT FROM AUTHOR]
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- 2021
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14. The prognostic role of tumor infiltrating T-lymphocytes in squamous cell carcinoma of the head and neck: A systematic review and meta-analysis.
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de Ruiter, Emma J., Ooft, Marc L., Devriese, Lot A., and Willems, Stefan M.
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HEAD & neck cancer ,SQUAMOUS cell carcinoma ,T cells ,PROGNOSIS - Abstract
Background– The presence of tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment is associated with an improved prognosis and a better response to therapy in different types of cancer. In this systematic review and meta-analysis, we investigated the prognostic value of T cells in head and neck squamous cell carcinoma (HNSCC). Methods– In a systematic review, Pubmed and Embase were searched for publications that investigated the prognostic value of T cells in HNSCC. A meta-analysis was performed including all studies assessing the association between CD3+, CD4+, CD8+, and FoxP3+ TILs and overall survival (OS), disease-free survival (DFS), or locoregional control (LRC). Results– A pooled analysis indicated a favorable, prognostic role for CD3+ TILs (HR 0.64 (95%CI 0.47–0.85) for OS, HR 0.63 (95%CI 0.49–0.82) for DFS) and CD8+ TILs (HR 0.67 (95%CI 0.58–0.79) for OS, HR 0.50 (95%CI 0.37–0.68) for DFS, and HR 0.82 (95%CI 0.70–0.96) for LRC) in the clinical outcome of HNSCC. FoxP3+ TILs were also associated with better OS (HR 0.80 (95%CI 0.70–0.92)). Conclusion– This systematic review and meta-analysis confirmed the favorable, prognostic role of CD3+ and CD8+ T cell infiltration in HNSCC patients and found an association between FoxP3+ TILs and improved overall survival. Future studies using homogeneous patient cohorts with regard to tumor subsite, stage and treatment are necessary to provide more insight in the predictive value of TILs in HNSCC. [ABSTRACT FROM PUBLISHER]
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- 2017
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15. Prognostic value of PSMA, c-MET and E-cadherin in salivary duct carcinoma.
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van Boxtel, Wim, Uijen, Maike J.M., Verhaegh, Gerald W., Willems, Stefan M., Jonker, Marianne A., Schalken, Jack A., van Engen-van Grunsven, Ilse C.H., van Herpen, Carla M.L., and PALGA Group
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ANDROGEN receptors , *CARCINOMA , *LYMPH nodes , *PROTEIN expression , *SALIVARY gland cancer - Abstract
Objectives: Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland cancer. Androgen receptor (AR) (96%) and HER2 (29-46%) expression, and a high propensity for regional lymph node metastases are hallmarks of the disease. We hypothesized that c-MET, E-cadherin, PSMA tumor and PSMA neovascular expression may be prognostic factors in SDC.Materials and Methods: Expression levels of these proteins were established on tissue microarrays containing 165 primary SDC tumor specimens. Association with survival was studied with Kaplan-Meier curves, and univariable and multivariable Cox regression models. Furthermore, association with lymph node status, AR and HER2 expression, and gender was studied.Results: We found that patients with high PSMA tumor expression showed a significantly longer overall survival (OS) (median 83 vs. 43 months, P = 0.022), a trend towards a longer DFS (median 51 vs. 22 months, P = 0.094), and significantly reduced hazard ratio for death in the univariable Cox regression model (HR 0.46, P = 0.034). In the multivariable model only a high number of tumor-positive lymph nodes and high age (>80) at diagnosis were prognostic for poor OS. High PSMA tumor expression was also significantly associated with low N-stage (P = 0.001) and expression was higher in women versus men (P = 0.029). High PSMA tumor expression and E-cadherin loss were significantly associated with strong and weak AR-expression, respectively (P = 0.033 and P = 0.007). None of the factors were significantly associated with HER2 expression.Conclusion: c-MET, E-cadherin, and tumor and neovascular PSMA expression are no independent prognostic factors in SDC. [ABSTRACT FROM AUTHOR]- Published
- 2020
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