Programmed cell death ligand‐1 protein expression and <i><scp>CD</scp>274/<scp>PD</scp>‐L1</i> gene amplification in colorectal cancer: Implications for prognosis

Abstract

Programmed cell death ligand-1 (PD-L1) detection assays have not been standardized for patients with colorectal cancer, and the prognostic value of PD-L1 expression is unclear. We compared the PD-L1 expression patterns in colorectal cancer samples using various immunohistochemical assays using 3 primary PD-L1 antibodies (assay 1, MIH1; assay 2, E1L3; and assay 3, 22C3) and investigated the prognostic implication of PD-L1 expression using each. Additionally, PD-L1 gene amplification was evaluated using FISH. The percentage scorings and positivity rates of the 3 assays differed; the degrees of correlation and concordance between assays 2 and 3 were relatively high, whereas assay 1 was an outlier. Multivariate analyses indicated that PD-L1 positivity in tumor cells and its negativity in tumor-infiltrating lymphocytes were independent predictors of poorer overall and disease-free survival in patients with colorectal cancer. PD-L1 gene amplification was found in 2 patients (PD-L1/CEP ratio, 5.60 and 5.84, respectively); both had strong PD-L1 expression according to immunohistochemistry. Overall, our study showed that PD-L1 expression status in tumor and immune cells is an independent prognostic factor in patients with colorectal cancer. Standardizations of both PD-L1 detection using immunohistochemistry and the cut-off for positivity are necessary. Finally, PD-L1 gene amplification was found in a small fraction of samples, suggesting the possibility of an ancillary test for PD-L1 evaluation.