Clinical Impact of Tumor-Infiltrating Lymphocytes for Survival in Stage II Colon Cancer

BACKGROUND: The most reliable prognostic factor in colon cancer is the TNM classification. The objective of this study was to assess and compare the prognostic role of tumor-infiltrating lymphocytes (TILs) in stage II colon cancer. METHODS: Immunohistochemistry was used to assess the density of TILs that were positive for cluster of differentiation 3 (CD3) (T-cell coreceptor), CD45 isoform RO (CD45RO) (protein tyrosine phosphatase), nuclear transcription factor forkhead box P3 (FOXP3), and CD25 (a type I transmembrane protein) according to tumor site (intraepithelial and stromal) in samples from 87 patients who had stage II colon cancer. These variables were evaluated for their association with histopathologic features along with overall survival (OS) and disease-free survival (DFS). RESULTS: Intraepithelial CD3-posititve (CD3+), CD45RO+, CD25+, and FOXP3+ TILs were associated significantly with better DFS (P = .049, P = .009, P = .013, and P = .001, respectively). The estimated 5-year OS rates for patients who had high-density CD45RO+ and FOXP3+ expression was 100% for both compared with 79.2% and 78.8% for patients who had low-density CD45RO+ and FOXP3+ expression (P = .017 and P = .040, respectively). A significant prognostic factor for both OS and DFS was high-density stromal CD45RO+ lymphocytic infiltration (OS: P = .031; relative risk [RR], 0.134; 95% confidence interval [CI], 0.015-1.164; DFS: P = .013; RR, 0.198; 95% CI, 0.055-0.710); whereas intraepithelial FOXP3+ expression was an independent prognostic factor for DFS (P = .032; RR, 0.108; 95% CI, 0.014-0.821). CONCLUSIONS: FOXP3+ and CD45RO+ TILs demonstrated independent prognostic significance for survival in the current investigation. These results may help to improve the prognostication of early stage colon cancer. Cancer 2010;116:5188-99. (c) 2010 American Cancer Society.