PD-L1 Expression and CD8+ Tumor-infiltrating Lymphocytes in Different Types of Tubo-ovarian Carcinoma and Their Prognostic Value in High-grade Serous Carcinoma. (August 2020)

• Record Type: Journal Article
• Authors: Chen, Hao; Molberg, Kyle; Strickland, Amanda L.; Castrillon, Diego H.; Carrick, Kelley; Jiang, Qingping; Niu, Shuang; Rivera-Colon, Glorimar; Gwin, Katja; Hinson, Stacy; Lea, Jayanthi; Miller, David S.; Zheng, Wenxin; Lucas, Elena
• Is Part Of: American journal of surgical pathology. Volume 44:Number 8(2020)
• Publication Date: 2020-08
• Subjects: PD-L1 -- ovary -- ovarian cancer -- tumor-infiltrating lymphocytes -- survival -- BRCA -- chemotherapy; Pathology, Surgical -- Periodicals; 617.0705
• DOI: 10.1097/PAS.0000000000001503
• Languages: English
• ISSNs: 0147-5185

Abstract

Abstract : The prevalence and significance of programmed death-1 ligand (PD-L1) expression in different types of tubo-ovarian carcinoma have not been well defined. We evaluated PD-L1 expression and CD8 + tumor-infiltrating lymphocyte (TIL) density in whole tissue sections of 189 cases of tubo-ovarian carcinoma, including high-grade serous carcinoma (HGSC, n=100), clear cell carcinoma (CCC, n=24), endometrioid carcinoma (EmC, n=40), and mucinous carcinomas (MC, n=25). Using the tumor proportion score (TPS) with a 1% cutoff, PD-L1 expression was present in 21% of HGSC, 16.7% of CCC, 2.5% of EmC, and 4% of MC. Using the combined positive score (CPS) with a cutoff of 1, PD-L1 expression was present in 48% of HGSC, 25% of CCC, 20% of EmC, and 24% of MC. HGSC demonstrated significantly higher CD8 + TIL density than CCC ( P =0.013238), EmC ( P =0.01341), or MC ( P =0.004556). In HGSC, CD8 + TIL density was directly correlated with PD-L1 positivity using either TPS ( P =0.0008) or CPS ( P =0.00011). Survival analysis of patients with high stage (stage III to IV) HGSC revealed PD-L1 positivity by TPS to be associated with improved progression-free survival (adjusted hazard ratio: 0.4912 vs. 2.036, P =0.0378). Although not statistically significant, a similar trend was observed in overall survival (adjusted hazard ratio: 0.3387 vs. 2.953, P =0.0548). In contrast, with CPS, no significant difference was identified between PD-L1-positive and negative groups in either progression-free survival ( P =0.5086) or overall survival ( P =0.7823). Neoadjuvant chemotherapy was associated with higher PD-L1 expression by TPS ( P =0.00407) but not CPS. No significant difference in PD-L1 expression was detected in tumors from patients with germline BRCA1/2 mutations compared with germline mutation-negative tumors by either TPS or CPS. In conclusion, the prevalence of PD-L1 expression is variable in different types of tubo-ovarian carcinoma and is highest in HGSC. In high-stage HGSC, PD-L1 positivity in tumor cells is associated with an increased immune response and improved survival.