PD-L1 Expression Is an Independent Marker for Lymph Node Metastasis in Middle Eastern Endometrial Cancer.

Nabil Siraj,Khawla S Al-Kuraya,Abdul K Siraj,Sandeep Kumar Parvathareddy,Fouad Al-Dayel,Padmanaban Annaiyappanaidu,Ismail A Al-Badawi,Maha Al-Rasheed

doi:10.3390/diagnostics11030394

Abstract

Programmed death ligand 1 (PD-L1) expression in endometrial cancer (EC) tumor cells have been reported in several studies with inconsistent results. Furthermore, there is scarcity of data on the prevalence and prognostic significance of PD-L1 expression in EC from Middle Eastern ethnicity. We aimed to assess PD-L1 expression in a large cohort of Middle Eastern EC and to correlate this with clinico-pathological factors, as well as mismatch repair (MMR) protein status and patients’ outcome. PD-L1 expression was investigated using immunohistochemistry on tissue microarray in an unselected cohort of 440 EC. Kaplan–Meier and logistic regression analysis were used to compare the outcome and prognostic factors. PD-L1 expression in tumor tissue was detected in 18.9% (83/440) EC cases with no impact on survival. When stratified for MMR protein status, PD-L1 expression was similar for both MMR deficient and MMR proficient ECs. However, the expression of PD-L1 in tumor cells was significantly associated with type II (non-endometrioid) histology (p = 0.0005) and lymph node metastasis (p = 0.0172). Multivariate analysis showed PD-L1 expression to be an independent risk factor for lymph node metastasis (odds ratio: 2.94; 95% CI: 1.26–6.84; p = 0.0123). In conclusion, PD-L1 was strongly associated with non-endometrioid EC and was an independent prognostic marker of lymph node metastasis.

Highlights

Endometrial cancer (EC) is the most common gynecological malignancy in the Western countries [1,2]
We evaluated the effect of programmed death ligand-1 (PD-L1) expression on overall survival (OS), recurrencefree survival (RFS), and disease-free survival (DFS)
A recent large metanalysis with more than 1600 patients suggested that PD-L1 expression is not associated with poor prognosis in endometrial cancer patients. They conclude that PD-L1 expression is positively correlated with poor differentiation and advanced stage in endometrial cancer [44]. These findings are in concordance with our study results, where we show that PD-L1 expression is strongly associated with lymph node metastasis

Summary

Introduction

Endometrial cancer (EC) is the most common gynecological malignancy in the Western countries [1,2]. In Saudi Arabia, EC is the most common gynecological cancer and the fourth most common cancer among Saudi women [3]. Recurrence and metastasis remain a challenge despite the available therapeutic options of surgery, chemotherapy, radiotherapy, and hormonal therapy. Immune checkpoint inhibitor has emerged as a promising therapeutic option in oncology and has significantly altered the standard treatment for many advanced cancers [8]. The most common mechanisms underlying immunotherapy are programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) which serve as immune checkpoints in tumor micro environment [9,10].

Objectives

Methods

Findings

Discussion

Conclusion