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 immunohistochemistry. 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.

Exome sequencing revealed comparable frequencies of RNF43 and BRAF mutations in Middle Eastern colorectal cancer

“…Tissue microarray (TMA) format was utilized for immunohistochemical analysis of samples. Construction of TMA was done as described previously 28 . Briefly, representative tumor regions from each donor tissue block were chosen and tissue cylinders with a diameter of 0.6 mm were punched and brought into recipient paraffin block with the help of a modified semiautomatic robotic precision instrument (Beecher Instruments, Wood-land, WI, USA).…”

Immune checkpoint blockade therapy for BRAF mutant metastatic colorectal cancer: the efficacy, new strategies, and potential biomarkers

“…Indeed, PD-L1 expression is found in only 9–15% of CRC patients [ 96 ]. Reports showed that upregulation of PD-L1 in CRC cells is associated with poorly differentiated and solid/medullary histology, MSI-H or dMMR, and BRAF mutations [ 95 , 97 , 98 ], signatures of the serrated neoplasia pathway of colorectal adenocarcinomas [ 99 ]. In tissue samples collected from 43 patients with colon cancer, Cen et al found that BRAF mutation colon cancer had significantly higher expression of PD-L1, PD-1, CTLA4, LAG3, and TIM3, which is consistent with data from 396 colon cancers from TCGA datasets [ 85 ].…”

Circ_0000052/miR‐382‐3p axis induces PD‐L1 expression and regulates cell proliferation and immune evasion in head and neck squamous cell carcinoma

“…PD‐L1 is expressed at different levels in various cancers and is associated with poor prognosis in melanoma, 6 NSCLC 7 and colorectal cancer. 8 However, the clinical implications of PD‐L1 expression vary across studies. The Pembrolizumab trial found that patients with ≥1% PD‐L1 expression had significantly better survival.…”

“…PD‐L1 (CD274 gene) is upregulated in many cell types, including cancer cells, in response to pro‐inflammatory cytokines. PD‐L1 is expressed at different levels in various cancers and is associated with poor prognosis in melanoma, 6 NSCLC 7 and colorectal cancer 8 . However, the clinical implications of PD‐L1 expression vary across studies.…”