Expression of interleukin-4 and interleukin-13 and their receptors in colorectal cancer

Int J Colorectal Dis. 2012 Oct;27(10):1369-76. doi: 10.1007/s00384-012-1456-0. Epub 2012 Mar 24.

Abstract

Purpose: Interleukin-4 (IL-4) and interleukin-13 (IL-13) are anti-inflammatory and immunomodulatory cytokines which can influence cancer-directed immunosurveillance. Nothing is presently known about expression of these cytokines and their receptors (IL-4R and IL-13R) in colorectal cancer. The aim of this study was to characterize their expression in primary colorectal cancer specimens and to evaluate possible functions for this disease.

Methods: Expression of IL-4, IL-13, IL-4R, and IL-13R protein was characterized by immunohistochemistry in 359 patients with Union for International Cancer Control stage I-III colorectal cancer and evaluated by uni- and multivariate analysis for their prognostic relevance.

Results: All four proteins were expressed in colorectal cancer specimens. In the cancer cells, high IL-4, IL-13, IL-4R, and IL-13R immunoreactivity were present in 33 % (118/359), 50 % (181/359), 36 % (129/359), and 42 % (152/359), respectively. Patients with high expression of IL-4, IL-4R, and IL-13R had a lower frequency of lymph node metastases. Expression of IL-13 did not influence the frequency of lymph node metastases. However, high IL-13-immunoreactivity was associated with a better overall survival (p = 0.041). Expression of IL-4, IL-4R, or IL-13R did not influence survival. Multivariate analysis revealed that besides pT classification and tumor recurrence, IL-13 expression was an independent prognostic factor for overall survival.

Conclusions: Expression of IL-4, IL-4R, and IL-13R are involved in the process of local metastases in colorectal cancer, while IL-13 expression has an impact on survival. These interleukins and their receptors may become attractive targets for the treatment of colorectal cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Interleukin-13 / metabolism*
  • Interleukin-4 / metabolism*
  • Interleukin-4 Receptor alpha Subunit / metabolism*
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Prognosis
  • Receptors, Interleukin-13 / metabolism*
  • Receptors, Interleukin-4 / metabolism*
  • Regression Analysis

Substances

  • IL4 protein, human
  • IL4R protein, human
  • Interleukin-13
  • Interleukin-4 Receptor alpha Subunit
  • Receptors, Interleukin-13
  • Receptors, Interleukin-4
  • interleukin-13 receptor, human
  • interleukin-13, human
  • Interleukin-4