CD8+ TILs in early stage epithelial ovarian cancer: A GEICO study.

Abstract

5543 Background: The extent of tumor infiltrating lymphocytes (TILs) has emerged as a potential clinical useful biomarker in epithelial ovarian cancer (OC); however differences in TILs among OC histological types have not been extensively analysed. Methods: From a prospective early stage (I-II) GEICO registry of 1151 cases, 573 were sent for central pathology review. Complete analysis for classification of OC correctly identified 488 cases. Histological typing was performed according to morphological features and the expression of WT1, p53, p16, estrogen receptor (ER), progesterone receptor, and napsin A. The expression of mismatch repair (MMR) proteins MLH1, PMS2, MSH2 and MSH6 was performed in all tumors. The absolute number of stromal and intraepithelial CD8+ TILs per 0.6 mm2 TMA core was quantified and correlated with pathological features. Results: The series included 127 high-grade serous carcinomas (HGSC) (26%), 22 low-grade serous carcinomas (LGSOC) (4.5%), 165 endometrioid carcinomas (EC) (33.8%), 124 clear cell carcinomas (CCC) (2.4%), and 50 mucinous carcinomas (MC) (10.2%). The mean of intraepithelial CD8+ TILs was higher in HGSG (48.7) than in all other histological types (LGSG: 16.3; EC: 27.1; MC: 7.0; and CCC 10.3; p<0.0001). In the stromal component, the mean of CD8+TILs was also higher in HGSG (31.1) than in EC, MC and CCC (15.8, 8.0 and 12.7, respectively; p<0.0001). The mean of intraepithelial CD8+ TILs was significantly higher in RE-positive (71.9) than in RE-negative (34.8) HGSC ( p=0.002). In the complete series, 33 (6.6%) OCs showed absent expression of at least 1 MMR protein, and the mean of intraepithelial CD8+ TILs was significantly higher in these OCs (57.0) than in those with preserved expression of all MMR proteins (23.6; p=0.0035). MMR protein deficiency was observed in 27 (16%) ECs, and these tumours had significantly higher mean of both intraepithelial (60.4 vs. 20.7 p=0.003) and stromal CD8+ TILs (26.6 vs. 13.8, p= 0.046). No significant differences in TILs were observed among EC of different histological grades. Conclusions: The extent of CD8+TILs significantly correlates with the histological type and MMR status in OCs, being HGSCs and EC with MMR deficiency those OCs with higher CD8+TILs.