title: Expression of interleukin-4 and interleukin-13 and their receptors in colorectal cancer.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of General, Visceral, and Transplantation Surgery, University of Ulm, Steinhövelstrasse 9, Ulm, Germany. andrea.formentini@uniklinik-ulm.de
authors.forename: Andrea
authors.initials: A
authors.lastname: Formentini
authors.forename: Philipp
authors.initials: P
authors.lastname: Braun
authors.forename: Harald
authors.initials: H
authors.lastname: Fricke
authors.forename: Karl-Heinrich
authors.initials: KH
authors.lastname: Link
authors.forename: Doris
authors.initials: D
authors.lastname: Henne-Bruns
authors.forename: Marko
authors.initials: M
authors.lastname: Kornmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018793:Interleukin-13 / Q000378:metabolism*; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000378:metabolism*; D053662:Interleukin-4 Receptor alpha Subunit / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D053660:Receptors, Interleukin-13 / Q000378:metabolism*; D019948:Receptors, Interleukin-4 / Q000378:metabolism*; D012044:Regression Analysis
chemical_list: C578095:IL13 protein, human; C508181:IL13RA1 protein, human; C508598:IL4 protein, human; C504000:IL4R protein, human; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D053662:Interleukin-4 Receptor alpha Subunit; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D015847:Interleukin-4