TY - JOUR
T1 - PD-L1 Expression and CD8#x0002B;Tumor-infiltrating Lymphocytes in Different Types of Tubo-ovarian Carcinoma and Their Prognostic Value in High-grade Serous Carcinoma
AU - Chen, Hao
AU - Molberg, Kyle
AU - Strickland, Amanda L.
AU - Castrillon, Diego H.
AU - Carrick, Kelley
AU - Jiang, Qingping
AU - Niu, Shuang
AU - Rivera-Colon, Glorimar
AU - Gwin, Katja
AU - Hinson, Stacy
AU - Lea, Jayanthi
AU - Miller, David S.
AU - Zheng, Wenxin
AU - Lucas, Elena
N1 - Publisher Copyright:
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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#x0002B; 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#x00025; cutoff, PD-L1 expression was present in 21#x00025; of HGSC, 16.7#x00025; of CCC, 2.5#x00025; of EmC, and 4#x00025; of MC. Using the combined positive score (CPS) with a cutoff of 1, PD-L1 expression was present in 48#x00025; of HGSC, 25#x00025; of CCC, 20#x00025; of EmC, and 24#x00025; of MC. HGSC demonstrated significantly higher CD8#x0002B; TIL density than CCC (P=0.013238), EmC (P=0.01341), or MC (P=0.004556). In HGSC, CD8#x0002B; 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.
AB - 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#x0002B; 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#x00025; cutoff, PD-L1 expression was present in 21#x00025; of HGSC, 16.7#x00025; of CCC, 2.5#x00025; of EmC, and 4#x00025; of MC. Using the combined positive score (CPS) with a cutoff of 1, PD-L1 expression was present in 48#x00025; of HGSC, 25#x00025; of CCC, 20#x00025; of EmC, and 24#x00025; of MC. HGSC demonstrated significantly higher CD8#x0002B; TIL density than CCC (P=0.013238), EmC (P=0.01341), or MC (P=0.004556). In HGSC, CD8#x0002B; 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.
KW - BRCA
KW - chemotherapy
KW - ovarian cancer
KW - ovary
KW - PD-L1
KW - survival
KW - tumor-infiltrating lymphocytes
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U2 - 10.1097/PAS.0000000000001503
DO - 10.1097/PAS.0000000000001503
M3 - Article
C2 - 32384321
AN - SCOPUS:85085003773
SN - 0147-5185
VL - 44
SP - 1050
EP - 1060
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 8
ER -