Pd‐l1 expression is associated with deficient mismatch repair and poor prognosis in middle eastern colorectal cancers

Abstract

Several clinical trials are investigating the use of immune‐targeted therapy with Programmed death ligand‐1 (PD‐L1) inhibitors for colorectal cancer (CRC), with promising results for patients with mismatch repair (MMR) deficiency or metastatic CRC. However, the prognostic significance of PD‐L1 expression in CRC is controversial and such data are lacking in CRC from Middle Eastern ethnicity. We carried out this large retrospective study to investigate the prognostic and clinico‐pathological impact of PD‐L1 expression in Middle Eastern CRC using immunohistochem-istry. A total of 1148 CRC were analyzed for PD‐L1 expression. High PD‐L1 expression was noted in 37.3% (428/1148) cases and was correlated with aggressive clinico‐pathological features such as high malignancy grade (p < 0.0001), larger tumor size (p = 0.0007) and mucinous histology (p = 0.0005). Interestingly, PD‐L1 expression was significantly higher in patients exhibiting MMR deficiency (p = 0.0169) and BRAF mutation (p = 0.0008). Furthermore, the expression of PD‐L1 was found to be an independent marker for overall survival (HR = 1.45; 95% CI = 1.06 − 1.99; p = 0.0200). In conclusion, the results of this study indicate that PD‐L1 expression could be a valid biomarker for poor prognosis in Middle Eastern CRC patients. This information can help in decision‐making for anti‐PD‐L1 therapy in Middle Eastern CRC, especially for patients with MMR deficient tumors.