The appearance of Tregs in cancer nest is a promising independent risk factor in colon cancer

J Cancer Res Clin Oncol. 2013 Nov;139(11):1845-52. doi: 10.1007/s00432-013-1500-7. Epub 2013 Sep 5.

Abstract

Purpose: To investigate the prognostic value of tumor-infiltrating regulatory T cells (Tregs) in the distribution of cancer nest, cancer stroma and normal mucosa and FOXP3-positive cancer cells in colon cancer patients after resection.

Methods: Paraffin blocks of operation resection of primary adenocarcinoma of colon were obtained from ninety patients. The distribution of tumor-infiltrating Tregs was detected by tissue microarray and immunohistochemistry staining technique to evaluate the prognostic effects by Kaplan-Meier and Cox regression analysis using median values as cutoff.

Results: The intratumoral Tregs counts were significantly higher than that in corresponding normal mucosa tissues (P < 0.001); the Tregs counts in cancer nest were significantly lower than that in corresponding cancer stroma tissues (P < 0.001); the increased intratumoral Tregs counts were associated with favorable prognosis (P < 0.05); the presence of Tregs in cancer nest was associated with unfavorable prognosis and was an independent prognostic factor for overall survival (P < 0.05). The appearance of FOXP3-positive cancer cells was associated with worse prognosis (P < 0.05). In addition, the frequency of the presence of FOXP3-positive cancer cells was higher in patients with lymphatic invasion (P < 0.001) and lower in patients with early TNM stage (P < 0.01).

Conclusions: The higher tumor-infiltrating Tregs counts are closely associated with the improved prognostic effects of colon carcinoma. Tregs play different roles in cancer nest and cancer stroma. And the appearance of Tregs in cancer nest is a promising independent risk factor for overall survival in colon carcinoma. FOXP3-positive cancer cells may also be a risk factor for overall survival in colon carcinoma.

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / pathology
  • Aged
  • Colonic Neoplasms / immunology*
  • Colonic Neoplasms / pathology
  • Female
  • Forkhead Transcription Factors / biosynthesis
  • Forkhead Transcription Factors / immunology
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Neoplasm Grading
  • Neoplasm Staging
  • Paraffin Embedding
  • Prognosis
  • Risk Factors
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology
  • Tissue Array Analysis

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors