PD-L1 Expression in colorectal carcinoma and its correlation with clinicopathological parameters, microsatellite instability and BRAF mutation

Abstract

Context: Programmed cell death ligand-1 (PD-L1) is the key inhibitor of the cytotoxic immune response thus causing progression of tumors and adverse prognosis in many malignancies. Objective: The current study investigates PD-L1 expression in colorectal carcinoma and its correlation with clinicopathological parameters, microsatellite instability, and BRAF mutation. Material and Methods: 110 cases of colorectal carcinoma were evaluated for PD-L1 expression using SP263 clone in tissue microarray. Clinico-pathological characteristics and survival data were correlated with PD-L1 expression analyzed at different cut-offs of ≥1%, ≥10% and ≥50% in tumor cells and tumor infiltrating lymphocytes along with its correlation with BRAF expression and microsatellite instability status in these cases. Results: Mean age was 49 years with male to female ratio of 1.5:1. 52.7% cases presented with stage 3/4 disease and 14.7% with >10 cm tumor size. Tumor cells expressed PD-L1 in 40% and TILs in 45.4% cases at a cut off of ≥1% was 17.3%, at ≥10% was 15.5% and at ≥50% was 7.3%. Significant association was seen between tumor proportion score (TPS) and increasing age, histological type, histological grade, tumor size, higher T stage (p = 0.03), TILs (p = 0.04), lymph vascular invasion, and perineural invasion. PDL-1 correlated with BRAF expression and microsatellite instability (MLH-1/PMS-2 expression loss). The overall survival was significantly higher (p < 0.001) with negative PDL1 expression in cases of colorectal carcinoma. Conclusions: Immunotherapy may be used as potential therapeutic option in colorectal carcinoma cases showing microsatellite instability and BRAF mutations which show poor response to conventional chemotherapy regimen and anti-EGFR therapy.