Differential Characteristics and Prognosis of PD-L1–Positive Endometrial Carcinomas: A Retrospective Chart Review

Abstract

Women with endometrial carcinomas that express PD-L1 may respond better to immunotherapy. Our aim was to investigate the differential characteristics of PDL1–positive endometrial carcinomas and the prognostic significance of PDL1. We performed a retrospective chart review of 231 women with endometrial carcinomas who were managed at King Hussein Cancer Center (2007–2016) and performed immunohistochemistry for MLH1, PMS2, MSH2, MSH6, p53, and PD-L1. Overall, 89 cases (38.5%) were MMR-deficient. PD-L1 was expressed in 49 cases (21.2%) and its expression was significantly associated with MLH1/PMS2 deficiency (p = 0.044) but not MSH2/MSH6 deficiency (p = 0.59). p53 was mutant in 106 cases (46.5%), and its mutation was significantly associated with MMR proficiency (p < 0.001) but not PDL1 expression (p = 0.78). In women with endometrioid adenocarcinomas, PD-L1 expression was significantly associated with the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) grade (p = 0.008). Overall, PDL1 expression did not significantly predict overall survival in unadjusted or adjusted analyses (p = 0.92 and 0.54, respectively). In conclusion, tumors with MLH1/PMS2 loss and high-grade endometrioid adenocarcinomas were more likely to express PDL1 in tumor cells. Further research is required to investigate whether the presence of either characteristic signals a higher likelihood of a favorable response if immunotherapy is administered.

Correlation of PD-L1 immunohistochemical expression with microsatellite instability and p53 status in endometrial carcinoma

“…Overall, 19.6% of cases were positive for PD-L1 (tumour cell positivity alone, 6.3%; immune cell positivity alone, 4.9%; both tumour cell and immune cell positivity, 8.4%). These findings are similar to those of a previous study where 21.2% of patients with EC were PD-L1 positive [10] . The percentage was higher in studies using high-grade carcinomas alone (30% in clear cell carcinomas and 50% in undifferentiated/dedifferentiated carcinomas) [8] , [9] .…”

“…Regarding the association of different combinations of marker expression with various clinicopathological parameters, combined PD-L1 positivity and MMR deficiency (MHL1 negative and/or MSH2 negative) was found to be correlated with LVSI. Previous studies found that combined PD-L1 positivity and MMR deficiency was associated with adverse findings, such as high tumour grade [10] ; therefore, there is a potential role for immunotherapy to benefit EC patients with MMR deficiency [6] , [7] , [9] , [12] . The association found between PD-L1 positivity and MMR deficiency in the present study was lower than reported previously [28] .…”

“…This could be translated into practice simply by testing POLE gene mutation, MSI and p53 status [4] . PD-L1 plays an important role in tumour immunology and cancer treatment, and studies have investigated the value of its expression in EC [8] , [9] , [10] .…”

“…Several studies have investigated PD-L1 expression and its prognostic values in EC [6] , [7] . However, many of these studies did not consider the correlation with mismatch repair gene expression and p53 status [6] , [7] , [10] . The poorer outcome for patients with aggressive EC, such as USC, using traditional treatment methods portends great importance in finding effective targeted immunotherapy.…”

Rare Subtype of Endometrial Cancer: Undifferentiated/Dedifferentiated Endometrial Carcinoma, from Genetic Aspects to Clinical Practice

“…Programmed death receptor (PD-1) and its ligand PD-L1 are known as important biomarkers for immune checkpoint inhibitors. As a co-inhibitory transmembrane receptor expressed by T cells, PD-1 can inhibit the proliferation, survival, and cytokine production of T cells by engaging with PD-L1 [ 40 ], resulting in immune escape. Extensive work has been undertaken to investigate PD-1 blockage in a variety of cancers, leading to clinical approval for treatment, for example, melanoma with pembrolizumab, and renal cell carcinoma with nivolumab [ 41 ].…”