Clinicopathologic Features and Prognostic Role of CD3, CD8, and PD-1 positive Tumor-Infiltrating Lymphocytes and the Association with COX-2 Overexpression in Endometrial Carcinoma

Abstract

Background: Determining prognostic factors of endometrial cancer is important for the management of this disease. Objectives: The aim of this study was to identify the association between tumor- infiltrating lymphocytes (TILs) and programmed cell death protein-1 (PD-1) expression in intra-tumoral inflammatory cells and clinicopathological features of endometrial carcinoma. Methods: This observational study was conducted on 56 patients who underwent hysterectomy with diagnosis of endometrial carcinoma and available 5-year follow-up data from 2006 to 2013 in Imam Khomeini Hospital, Tehran, Iran. The TILs scoring was calculated based on the mean percentage of stroma occupied by mononuclear inflammatory cells at the invasive border of the tumor in H & E stained slides in 10 representative high-power fields. The mean number of CD3, CD8, and PD-1 positive lymphocytes in 10 high-power fields, as well as cyclo-oxygenase-2 (COX-2) expression, were assessed. Results: TILs were significantly higher in endometrioid carcinoma compared to non-endometrioid carcinomas (P = 0.001). There was no significant association between TILs percentage, myometrial invasion, lymphovascular invasion, and tumor grade (P > 0.05). High TILs tumors showed better prognosis (P = 0.046). On the immunohistochemical (IHC) study, TILs were higher in endometrioid tumors compared to non-endometrioid tumors (P < 0.05). The expression of PD-1 was higher in endometrioid tumors compared to non-endometrioid carcinomas (P = 0.001). The COX-2 expression was not associated with prognosis and the other clinicopathologic features. Conclusions: High TILs and PD-1 expression were associated with better prognosis in endometrial carcinoma. Endometrioid carcinomas had a higher TILs, CD3, CD8, and PD-1 lymphocytes. This study failed to identify a clinically significant cut off for these inflammatory biomarkers.