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Relationships of genetic subgroups, tumor microenvironment, lag-3 immune checkpoint inhibitor expressed in t cells, and expression of vista, pd-l1, and gal-3 molecules that regulate t cells expressed in tumor cells with prognostic factors in endometrial cancers

2021
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Advisor: Prof. Dr. Özlem Erdem

Abstract (EN)

Endometrial cancers are the most common tumors in the female genital tract. Although most endometrial cancers are diagnosed at an early stage, tumors diagnosed at an advanced stage have a poor prognosis. The traditional dual classification system has been incomplete for predicting the prognosis of endometrial cancers and evaluating treatment alternatives. With the TCGA study, it was desired to decide on the treatment approaches by determining the prognosis of the tumors according to their molecular characteristics. These subgroups determined in the TCGA study; POLE ultramutated, MSI hypermutated, copy number low and high groups.Identifying the characteristics of the tumor microenvironment has increasing importance in determining prognosis and immunotherapy targets. Immunotherapy is frequently used in various tumor types. The expression of immune checkpoint molecules in endometrial carcinomas has been researching. Studies have been conducted on POLE ultramutated and MSI hypermutated subgroups, expressing immune checkpoint molecules in higher amounts and tumors in these genetic subgroups may benefit more from immunotherapy. In our study, possible genetic subgroups that can be determined by immunohistochemical studies in 529 endometrial carcinoma cases were determined (MSI hypermutated and copy number high/TP53 mutated group), the relationship of these subgroups with clinical and histopathological features was investigated. MSI was found in 31.8%, mutant type p53 expression was found in 13.9% of the cases. The tumor microenvironment was evaluated with CD3, CD8 and CD163, and the relationship of PD-L1, VISTA, LAG-3 and GAL-3 expressions with clinical, histopathological features and two possible genetic subgroups were compared. Our study includes a large number of cases. Studies investigating tumor microenvironment, VISTA, LAG-3 and GAL-3 expression in endometrial carcinomas are limited. Therefore, our study contributed to the literature in determining the target patient group for endometrial carcinomas that can receive immunotherapy.

Author

Dr. Dilara İrem Arslan Kahraman

How to Cite

Dilara İrem Arslan Kahraman (Medical Specialty Thesis). Relationships of genetic subgroups, tumor microenvironment, lag-3 immune checkpoint inhibitor expressed in t cells, and expression of vista, pd-l1, and gal-3 molecules that regulate t cells expressed in tumor cells with prognostic factors in endometrial cancers, 2021, Gazi University.

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