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

Background: Determination of prognostic factors of endometrial cancer is important for the management of this disease. The aim of this study was to identify the association between tumor infiltrating lymphocytes (TILs) and cyclo-oxygenase-2 (COX-2) overexpression with prognosis and clinicopathological features of endometrial carcinoma.Materials and methods: This observational study was conducted on 56 hysterectomy patients with endometrial carcinoma with 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 invasive border of the tumor in hematoxylin and eosin (H&E) staining in 10 representative fields. The mean number of Cluster of differentiation (CD) 3, CD8 and programmed cell death protein 1 (PD-1) positive lymphocytes in 10 representative high-power fields at the invasive border of tumor, intratumoral stroma and between the tumor cells were assessed. The association with clinicopathological features, 5-year survival and COX-2 overexpression was finally determined. 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 showed better prognosis (P = 0.046). On immunohistochemistry study, TILs was higher in endometrioid tumors compared to non-endometrioid tumors (p <0.05). Expression of PD-1 was higher in endometrioid tumors compared to non-endometrioid carcinomas (p = 0.001). COX-2 overexpression was not associated with prognosis and the other clinicopathologic features.Discussion: High TILs and PD-1 expression were associated with better prognosis in endometrial carcinoma. Endometrioid carcinomas had a higher TILs, CD3 and CD8 positive lymphocytes.

Keywords:

Tumor infiltrating lymphocyte , Endometrial cancer , Prognosis.