Validation of mesothelin as a marker and therapeutic target of epithelial ovarian cancer

Lemstra, F.L. (2013) Validation of mesothelin as a marker and therapeutic target of epithelial ovarian cancer. thesis, Medicine.

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Abstract

Rationale: Ovarian cancer (OC) is the most lethal gynecological cancer with 900 women dying each year in the Netherlands. Current treatment of surgery and chemotherapy does not prevent the disease from recurring in the majority of patients. In other words we need new therapeutic and diagnostic strategies and immunotherapy has shown promising results in (pre)clinical studies. The immune system and most importantly T lymphocytes are able to recognize tumor cells. Mesothelin is a potential target antigen for new innovative therapies and might also serve as prognostic marker in ovarian cancer. Aim: The primary aim of this study was to determine if the membrane glycoprotein mesothelin can be used as a prognostic factor in ovarian cancer. Secondary aim was to determine the relationship between mesothelin expression, tumor and patient characteristics and presence of cytotoxic T cells. Methods: Paraffin embedded tumor tissue was available from 339 OC patients diagnosed and treated at the University Medical Centre Groningen between 2000 and 2012. The pathology reports of all patients were examined and clinical information was extracted for the database. Next tissue blocks were selected to construct a Tissue Micro Array (TMA). Construction of the TMA was not part of this scientific rotation. An already existing TMA with 365 patients was used for immunohistochemical staining for mesothelin. Kaplan Meier curves were used to estimate survival outcomes. Log rank test was used to evaluate survival differences between groups. Pearsons Chi square test was used to test associations between mesothelin expression, presence of cytotoxic T cells and tumor and patient parameters. A multivariate Cox proportional hazard model was constructed to adjust for well-known prognostic markers. Results: The new TMA will consist out of 339 patients including 188 serous ovarian cancer cases. The disease specific survival (DSS) of patients with stage I disease was 131.6 months compared to a DSS of 69.6, 46.4 and 24.6 months in stages II, III and IV, respectively. Next, mesothelin expression, determined on the already existing TMA was detected in 72 out of 139 patients. High mesothelin expression was associated with a lower DSS(p=0.036) The Cox proportional hazard model suggested that mesothelin expression is not an independent prognostic factor. (p=0.35) Conclusion: Mesothelin is a potential new target antigen for the immune system being expressed in more than half of the patients with OC. Next, mesothelin might be used as prognostic marker in OC.

Item Type:	Thesis (Thesis)
Supervisor name:	Supervisor: and H.W. Nijman, Prof. dr. and Department Gynaecology Oncology and Researchline Tumorimmunology and Immunotherapy of Gynaecolog
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:48
Last Modified:	25 Jun 2020 10:48
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/918

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