Prognostic value of PD-L1 expression in colorectal cancer.

Abstract

610 Background: Growing evidence have shown promise for targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling in several tumors. However, the role of PD-L1 expression in colorectal cancer (CRC) tumor cells and its interaction with other clinicopathologic factors remain elusive. Methods: We constructed a tissue microarray with paraffin-embedded primary colon cancer tissue (n=103; stage I, 22; II: 44; III: 37). Expression levels of biomarkers (PD-L1, EGFR, p53, Ki67, LEF1, VEGF, COX2, MMR – by IHC, and MiR-34a - by in situ hybridization), clinicopathologic variables and clinical outcomes were investigated. H-score evaluation of PD-L1 was performed. Tumors with an H score >55, derived using Cutoff Finder, were considered PD-L1 positive for use in Kaplan-Meier survival analysis with log-rank test and in Cox regression models for recurrence-free survival (RFS) and overall survival (OS). Results: Median follow-up time for the entire cohort was 4.7 years (range 0.1-20.8). Positive PLD1 was identified in 89% of cases. As a group, cases with positive PD-L1 expression had better OS than those with negative expressions (12.2 vs 3.3 years) (p = 0.043), especially in cases with mismatch repair proficiency (MMR-P, 12.1 vs 1.0 years) (p <0.001). Negative PD-L1 expression in cases who had no chemotherapy was associated with worse outcome for OS (p=0.001) and RFS (p=0.008). There was no significant association between PD-L1 expression and gender, age, tumor size, pathologic stage or tumor grade. However, PD-L1 expression was significantly associated with MiR-34a (p<0.001) and p53 overexpression (p=0.008) with a trend toward association in cases with mismatch repair proficiency (MMR-P, p=0.053). Conclusions: Our results suggest that negative PD-L1 expression appears to have negative prognostic value with worse RFS and OS in stage I - III CRC patients, especially those who had not received any chemotherapy. Given a recent study suggesting p53/miR-34a/PD-L1 axis as a novel mechanism of immune evasion, and strong correlation in the PD-L1/p53 and PD-L1/miR-334a expressions in our cohort, further investigation of their interactions is warranted that may lead to identifying their predictive value for immuno/chemotherapy.