PD-L1 Expression in Endometrial Serous Carcinoma and Its Prognostic Significance

Abstract

Purpose Programmed death-ligand 1 (PD-L1) has been widely used as a prognostic biomarker and an immunotherapeutic target in numerous cancers, but information on the clinical significance of its expression in endometrial serous carcinoma (ESC) is largely lacking. Here, we evaluate the predictive value of PD-L1 expression in ESC. Materials and Methods A total of 79 cases of ESC accessioned between January 2003 and September 2015 were selected for further analysis. PD-L1 expression was evaluated in whole tissue sections of these cases by using the tumor proportion score (TPS, cut-off 1%) and combined positive score (CPS, cut-off 1) scoring methods. Results Overall, there was a heterogeneous expression of PD-L1, focal or patchy, in ESCs. PD-L1 positivity was observed in 43.0% of ESCs by TPS and 73.4% of ESCs by CPS. Kaplan–Meier survival analysis showed that patients with PD-L1-positive tumors suffered significantly worse OS and PFS, when compared with PD-L1 negative tumors (log-rank p = 0.037 and p = 0.003, respectively). In contrast, PD-L1 positivity by CPS within the ESC cases showed no statistical significance for OS and PFS (log-rank p = 0.720 and p = 0.928, respectively). Multivariate Cox analysis showed that PD-L1 positivity by TPS was significantly associated with PFS (HR = 1.921, p = 0.039) but not OS (HR = 1.229, p = 0.631). Conclusion PD-L1 expression is frequently found in ESC, suggesting a potential role of the PD-1/PD-L1 pathway as a potential therapeutic target for these tumors. PD-L1 expression by TPS also serves as a negative prognostic marker in ESC and implies an unfavorable outcome.

Overall survival prediction models for gynecological endometrioid adenocarcinoma with squamous differentiation (GE-ASqD) using machine-learning algorithms

“…The combination of PARP inhibitors and immune checkpoint inhibitors considerably improves the prognosis of gynecologic cancer patients and promotes the long-term benefits following maintenance therapy in the era of personalized precision medicine where targeted and immunotherapy are common 14 . Furthermore, Zhang et al and Chen et al demonstrated the predictive importance of PD-L1 expression in endometrial serous cancer 15 , 16 .…”

Targeting DNA Damage Repair and Immune Checkpoint Proteins for Optimizing the Treatment of Endometrial Cancer

“…Immunotherapy currently represents an attractive strategy for patients with EC, mainly those with advanced or recurrent disease, with no effective treatment options available after standard chemotherapy [ 93 ]. Given the high expression of PD-1/PD-L1 in EC, it is reasonable to test inhibitors targeting the PD-1-PD-L1 axis to treat EC [ 94 ]. Indeed, many studies have tested the efficacy of PD-1 or PD-L1 antibodies in different molecular subtypes of ECs.…”

Mesonephric-like Adenocarcinoma of the Uterine Corpus: Genomic and Immunohistochemical Profiling with Comprehensive Clinicopathological Analysis of 17 Consecutive Cases from a Single Institution

“…PD-L1 expression on tumor and immune cells can be detected using IHC and different PD-L1 commercial clones. PD-1 and PD-L1 play progressively important roles in our understanding of tumor immunology and antitumor treatment [ 19 ]. Binding of PD-L1 to its receptor PD-1 leads to T-cell inactivation in a variety of carcinomas [ 20 ].…”

“…Binding of PD-L1 to its receptor PD-1 leads to T-cell inactivation in a variety of carcinomas [ 20 ]. Therefore, anti-PD-1/PD-L1 treatment deregulates the adverse impact of tumor-infiltrating T-cells, which in turn may reverse the tumor immune resistance [ 19 ]. Several clinical and experimental studies have investigated PD-L1 expression in EC and its prognostic values as well as its efficacy as an immunotherapy for EC [ 21 , 22 , 23 ]; however, these studies focused on endometrioid carcinomas and did not consider MLA as a separate or independent group.…”