The Ratio of Intra-Tumoral Regulatory T Cells (Foxp3+)/Helper T Cells (CD4+) Is a Prognostic Factor and Associated With Recurrence Pattern in Gastric Cardia Cancer

Background: TILs have been reported to be a prognostic factor in human cancers. We assessed the prognostic significance of tumor-infiltrating regulatory T cells in gastric cardia cancer. Methods: We retrospectively reviewed the database of Severance Hospital for patients who underwent curative resection of gastric cardia cancer from Jan 2000 to Dec 2006 and identified 180 patients. Immunohistochemistry for TIL subsets was performed against CD3, CD4, CD8, Foxp3, and granzyme B in the resected tumor specimens. The absolute numbers and relative ratios of positively stained lymphocytes for each subset were evaluated. Results: A high Foxp3/CD4 ratio was identified as an unfavorable prognostic factor for overall survival (OS) using univariate and multivariate analysis of all immunologic variables. Patients group with high Foxp3/CD4 ratio was associated with loco-regional recurrence (P = 0.033). In multivariate analysis for clinical and immunologic variables, the nodal status (hazards ratio-HR: 3.863, confidence interval-CI: 1.664- 8.966, P = 0.002), depth of invasion (HR: 3.607, CI: 1.443-9.019, P = 0.006), and Foxp3/CD4 ratio (HR: 1.812, CI: 1.022-3.212, P = 0.042) were identified as independent prognostic factors for OS. Conclusions: A higher regulatory T cells/helper T cells ratio is associated with an unfavorable prognosis and loco-regional recurrence pattern in gastric cardia cancer. J. Surg. Oncol. 2011;104:728-733. (C) 2011 Wiley Periodicals, Inc.