Contrasting Prognostic Effects of Tumor-Infiltrating Lymphocyte Density in Cardia and Non-cardia Gastric Adenocarcinomas

PURPOSE: This study sought to investigate the prognostic significance of tumor-infiltrating lymphocytes (TILs) in relation to tumor location within the stomach. MATERIALS AND METHODS: The densities and prognostic significance of TIL subsets were evaluated in 542 gastric cancer patients who underwent gastrectomy. Immunohistochemical staining for CD3, CD4, CD8, forkhead/winged helix transcription factor (Foxp3), and granzyme B was performed. RESULTS: Cardia cancer was associated with significantly lower densities of CD8 T-cells and higher densities of Foxp3 and granzyme B T-cells than non-cardia tumors. Multivariate analysis showed that advanced age (hazard ratio [HR], 1.023; 95% confidence interval [CI], 1.006–1.040), advanced T classification (HR, 2.029; 95% CI, 1.106–3.721), lymph node metastasis (HR, 3.319; 95% CI, 1.947–5.658), low CD3 expression (HR, 0.997; 95% CI, 0.994–0.999), and a high Foxp3/CD4 ratio (HR, 1.007; 95% CI, 1.001–1.012) were independent predictors of poor overall survival in cardia cancer patients. In non-cardia cancer patients, total gastrectomy (HR, 2.147; 95% CI, 1.507–3.059), advanced T classification (HR, 2.158; 95% CI, 1.425–3.266), lymph node metastasis (HR, 1.854; 95% CI, 1.250–2.750), and a low Foxp3/CD4 ratio (HR, 0.978; 95% CI, 0.959–0.997) were poor prognostic factors for survival. CONCLUSIONS: The densities and prognostic effects of TILs differed in relation to the location of tumors within the stomach. The contrasting prognostic effects of Foxp3/CD4 ratio in cardia and non-cardia gastric cancer patients suggests that clinicians ought to consider tumor location when determining treatment strategies.