Programmed cell death ligand‐1 protein expression and CD274/PD‐L1 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.

Clinicopathological significance and prognostic implication of programmed death-1 ligand 2 expression in colorectal cancer

“…17 Among four studies on CRC, Zhu et al 18 reported that CRC patients that expressed PD-L1 had better survival rates. Lee et al 19 recently reported similar results. In our study, PD-L2 expression was significantly correlated with better survival.…”

“…Lymphocytic infiltrations are frequently identified in the colorectum, and the prognostic implication of TILs in CRC is well understood. [20][21][22] Although TILs are significantly correlated with PD-L1 expression, 19 the correlation between PD-L2 expression and TILs has not been fully elucidated in CRC. Masugi et al 2 studied the correlation between PD-L2 expression and lymphocytic reaction in CRC.…”

Targeting intermittent hypoxia downstream pathways for biomarker discovery and new treatment perspectives in cutaneous melanoma

“…Regarding the value of PD-L1 as a prognostic marker of cancer evolution, recent data have shown that increased PD-L1 expression is associated with unfavourable outcome in various cancers, but there are conflicting reports regarding its prognostic value in others, such as colorectal cancer [26]. This discrepancy can be attributed to technical issues but also to the origin and form of PD-L1 investigated.…”

“…For instance, expression of PD-L1 by tumour cells and by tumour-infiltrating immune cells has opposite effects on colorectal cancer aggressiveness and metastasis [26]. Moreover, studies investigating the role of PD-L1 on cancer development should distinguish membrane PD-L1 expressed by tumour and immune cells from plasma sPD-L1 and other circulating PD-L1 sources [27].…”

Identification of Prognostic Dosage-Sensitive Genes in Colorectal Cancer Based on Multi-Omics

“…Therefore, the copy number of dose-sensitive genes is more likely to be used as a driver gene in cancer. Some of the dosage-sensitive genes (DSGs) such as CD274/PD-L1 gene amplification (Lee et al, 2018b), fibroblast growth factor 1 amplification (Bae et al, 2019), RING-Finger Protein 6 amplification (Steinman et al, 1979), have been shown to be associated with poor prognosis, suggesting DSGs can also be considered as prognostic markers.…”