Clinicopathological and prognostic significance of PD-L1 expression in colon adenocarcinoma tumor budding

Abstract

Objective: In this study, we investigated the relationship between programmed cell death ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1) expression in colon adenocarcinoma tumor budding.

Methods: This study included 122 patients with colon adenocarcinomas. The largest sample of formaldehyde-fixed paraffin-embedded tumor tissues was selected for analysis. Expression of membranous PD-L1 (clone 22C3) and the Combined Positive Score (CPS) in tumor tissues was calculated and graded according to the percentages of peritumoral and intratumoral tumor cells (0 %, 1 %, 1-5 %, >5 %). The effects of these factors on the prognosis were analyzed.

Results: Tumor budding was associated with adverse clinicopathological features and poor overall survival. PD-L1 (CPS%) peritumoral tumor budding (1 %/<1 %) was statistically significant in the univariate model (p = 0.004). Age, organ metastases (liver, lung, liver, lung, and peritoneum), and metastases were statistically significant in the multivariate model (p = 0.001, p = 0.004, p = 0.001, p = 0.002, p = 0.004, and p = 0.032, respectively). PD-L1 positive staining was mostly observed around the tumor and during tumor budding. PD-L1 peritumoral tumor budding rates and patients' survival rates differed significantly (log-rank = 12.07, p = 0.007).

Conclusion: We found that patients with PD-L1 (CPS%) > 1 % in tumor budding had a shortened life expectancy and demonstrated the importance of including tumor budding areas in the samples used for biomarker evaluation. We previously reported that PD-L1 expression in tumor budding is associated with more aggressive cancer biology and poor survival, although overall survival is of limited statistical significance.

Keywords: Colon cancer; Combined Positive Score (CPS); Pathology; Prognosis; Programmed cell death ligand 1 (PD-L1); Tumor budding.