Interleukin-17-producing cell infiltration in the breast cancer tumour microenvironment is a poor prognostic factor

Histopathology. 2013 Aug;63(2):225-33. doi: 10.1111/his.12156. Epub 2013 Jun 6.

Abstract

Aims: Interleukin-17 (IL-17) is a proinflammatory cytokine that is most prominently produced by T-helper type 17 (Th17) cells, a distinct CD4+ T-helper cell subset. The aim of this study was to investigate the level of IL-17-producing cells in the breast cancer tumour microenvironment and its prognostic role.

Methods and results: A total of 207 breast carcinoma specimens were assessed by IL-17 immunohistochemistry, and the findings were correlated with clinicopathological parameters. We found that increased numbers of IL-17-producing cells were correlated with high histological grade, negative ER/PR status, and triple-negative molecular subtypes segregated by immunoprofiles. However, they did not correlate with stage, tumour size, nodal status, HER2 status, or histological type. Patients with tumours with high numbers of IL-17-producing cells had shorter disease-free survival (DFS) than patients with tumours with low numbers of IL-17-producing cells (P < 0.01). In multivariate analysis, high IL-17 level [hazard ratio (HR) 2.24; 95% CI 1.06-4.75], advanced T stage (HR 2.73; 95% CI 1.30-5.73), positive HER2 status (HR 4.88; 95% CI 1.47-16.18) and triple-negative subtype (HR 7.46; 95% CI 1.38-40.36) were significant prognostic factors for DFS.

Conclusions: Our results indicate that a high level of IL-17-producing cells in the breast cancer tumour microenvironment is a poor prognostic factor.

Keywords: breast cancer; inflammation; interleukin-17; prognosis; tumour microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology*
  • Disease-Free Survival
  • Female
  • Humans
  • Interleukin-17 / biosynthesis*
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / pathology*
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Th17 Cells / immunology*
  • Th17 Cells / pathology*
  • Tumor Microenvironment / immunology
  • Young Adult

Substances

  • Interleukin-17
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2