Monitoring EBV infection, MSI, PDL-1 expression, Her-2/neu amplification as a biomarker for PD-1 inhibition in gastric cancer
Abstract
BACKGROUND: The anti-PD-1 monoclonal antibody pembrolizumab has been shown to be associated with a good response in patients with metastatic gastric cancer. Excellent therapeutic results of pembrolizumab have been shown in patients with tumours showing a high microsatellite instability (MSI) and Epstein-Barr virus (EBV) positivity.
GOAL: This is a retrospective study of 40 bioptic specimens from the patients, who underwent gastrectomy for gastric carcinoma. The goal of the study was to identify biomarkers (EBV, MLH-1, PDL-1 expression) that are potentially relevant for selecting the patients, who may benefit from PD-1 inhibition therapy.
METHODS: Immunohistochemical (IHC) expression of PDL-1 and MSI, cytogenetic FISH amplification of the HER-2/neu gene and polymerase chain reaction of EBV RNA, including charge quantification, were performed in selected patients with metastatic or advanced gastric cancer. RESULTS: EBV-encoded RNA was detected in nine patients.
None of them exhibited Her-2 overexpression or CMV infection. PD-L1 was detected in twelve patients.
Ten patients were MLH1 positive. All nine cases of EBV infection showed a high expression of PD-L1 and MLH-1.