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

Abstract

: 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. The current study investigates PD-L1 expression in colorectal carcinoma and its correlation with clinicopathological parameters, microsatellite instability, and BRAF mutation. 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. 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. 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.