PD-L1 (22C3) expression and prognostic implications in esophageal squamous cell carcinoma

Abstract

Programmed cell death-ligand 1 (PD-L1) clone 22C3 is the only Food and Drug Administration-approved companion diagnostic test for pembrolizumab for the treatment of esophageal squamous cell carcinoma (ESCC). However, prior studies conducted in Asia and Europe have used various PD-L1 antibody clones other than 22C3. We aimed to study the expression profile of PD-L1, specifically of clone 22C3, in ESCC and its significance with regards to histological features, clinical parameters, and overall survival in a case series from two large US hospital systems. PD-L1 (22C3) immunohistochemistry was performed on 82 specimens obtained from 75 patients. Electronic medical records were reviewed to obtain the clinical and follow-up data. Of these specimens, 39 % (32/82) were negative for PD-L1 (22C3) expression (combined positive score (CPS) of 0). The remaining 50 specimens were positive, with CPSs ranging from 1 to 100. Treated specimens showed decreased PD-L1 (22C3) expression compared to untreated specimens. In the multivariate Cox proportional hazards regression model, PD-L1 (22C3) expression was shown to be a favorable prognostic factor for overall survival (p = 0.03, hazard ratio 0.16) only when the CPSs were ≥ 25, independent of surgery, definitive chemotherapy and/or radiotherapy, immunotherapy, and initial clinical stages. We performed a comprehensive study to investigate the expression profile of PD-L1 clone 22C3 in the US patients with ESCC. Our analysis showed that PD-L1 (22C3) expression decreased in treated specimens, and a CPS of ≥25 was associated with a favorable prognosis.