Tumor budding in gastric adenocarcinoma; reflections on tumor microenvironment and programmed death ligand 1 (PD-L1) expression

Introduction: The significance of tumor budding and programmed death ligand 1 (PD-L1) has not been established in gastric adenocarcinoma (GAC). Objectives: This study evaluated tumor budding and PD-L1 expression with regard to tumor microenvironment, clinicopathologic parameters, and overall survival in GAC. Patients and Methods: Totally, 102 GAC cases were assessed immunohistochemically. The associations of tumor budding and PD-L1 with clinicopathologic features, tumor-infiltrating lymphocytes (TILs), tumor stroma percentage (TSP), and overall survival were analyzed. Results: High tumor budding (42.2% of cases) was correlated with distal tumor location, large tumor size, Helicobacter pylori infection, poor differentiation (P = 0.0008, 0.033, 0.011, and 0.005, respectively), lymphovascular invasion, high tumor and nodal stages, and TSP (all P < 0.0001). Tumor budding was highest in the low TILs/high TSP group. PD-L1 expression (43.1% of cases) was correlated with proximal location (p = 0.00021), poor differentiation (P = 0.036), N stage (P = 0.049), high TILs (P < 0.0001), and low tumor budding (P = 0.002). PD-L1 expression was highest in the low tumor budding / high TILs category (P < 0.0001). Cox regression showed that high tumor budding (hazard ratio [HR]: 15.282, P = 0.024, 95% confidence interval [CI]: 1.441-162.069) and positive PD-L1 (HR: 7.502, P = 0.015, 95% CI: 1.469-38.31) were independent prognostic factors for overall survival. Conclusion: Tumor budding is correlated with poor prognostic parameters, whereas PD-L1 expression is inversely correlated with tumor budding. Both are independent predictors of short overall survival. Anti-PD-L1 immunotherapy could be effective in GAC with nodal metastasis, especially cases with high TILs and low tumor budding.