Abstract

Background and Objectives: Ovarian cancer is the leading cause of death among gynecological tumors. PD-1/PD-L1 immunoregulatory mechanism is activated in ovarian cancers. Lymphocyte infiltration is a significant factor that affects its expression. We analyzed the correlation between localization of lymphocytic infiltrate and PD-L1 expression in epithelial ovarian tumors. Materials and Methods: PD-L1 expression was analyzed in 328 subjects, 122 with epithelial ovarian carcinoma, 42 with atypical proliferative tumor, and 164 with benign epithelial ovarian tumor. Expression in central and invasive tumor parts in epithelial ovarian carcinoma was combined with the most pronounced lymphocyte reaction. Immunohistochemical analysis was performed using the tissue microarray and correlated with a set of histopathology parameters. Results: PD-L1 expression was most prominent in epithelial ovarian carcinoma with different levels of expression observed between invasive and central tumor segments. A high level of PD-L1 expression on tumor cells was more frequently present in the invasive than in the central tumor parts (p < 0.001) only in high-grade serous ovarian carcinoma (HGSC). There was no significant correlation between peritumoral lymphocytic infiltrate and PD-L1 expression regardless of tumor segment. In the central tumor parts of HGSC, there was a correlation of intratumoral lymphocytic infiltrate with a higher level of PD-L1 expression (p = 0.003). Conclusions: The most prominent PD-L1 expression was observed in the invasive tumor parts of HGSC. Only the central parts of the HGSC exhibited significant PD-L1 expression in association with considerable intratumoral lymphocytic infiltrate.

Highlights

  • The study included women with epithelial ovarian tumors classified into three study groups (Table 1)

  • Our study showed a significantly higher level of programmed death-ligand 1 (PD-L1) expression in Epithelial ovarian cancer (EOC) than in atypical proliferative tumor (ATP) tumors or in controls, indicating that the PD-1/PD-L1 immunoregulatory mechanism is activated in EOCs, most frequently in highgrade serous ovarian carcinoma (HGSC)

  • Our study reports about the significance of the tumor microenvironment and antitumoral immune response, which is more expressed in advanced Federation of Gynecology and Obstetrics (FIGO) stages and more aggressive histological EOC types (HGSC)

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Summary

Introduction

Epithelial ovarian cancer (EOC) has the highest mortality rate among all gynecological tumors. We analyzed the correlation between localization of lymphocytic infiltrate and PD-L1 expression in epithelial ovarian tumors. Expression in central and invasive tumor parts in epithelial ovarian carcinoma was combined with the most pronounced lymphocyte reaction. Results: PD-L1 expression was most prominent in epithelial ovarian carcinoma with different levels of expression observed between invasive and central tumor segments. A high level of PD-L1 expression on tumor cells was more frequently present in the invasive than in the central tumor parts (p < 0.001) only in highgrade serous ovarian carcinoma (HGSC). In the central tumor parts of HGSC, there was a correlation of intratumoral lymphocytic infiltrate with a higher level of PD-L1 expression (p = 0.003). The central parts of the HGSC exhibited significant PD-L1 expression in association with considerable intratumoral lymphocytic infiltrate

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