Elevated Interleukin-13 Receptor Alpha 1 Expression in Tumor Cells Is Associated With Poor Prognosis in Patients With Invasive Breast Cancer

Ann Surg Oncol. 2017 Nov;24(12):3780-3787. doi: 10.1245/s10434-017-5907-2. Epub 2017 Jun 20.

Abstract

Background: Interleukin (IL)-13 is an immunoregulatory, anti-inflammatory cytokine that is produced by numerous immune cells, and plasma membrane receptor for IL-13 (IL-13R) is known to be expressed in various human malignancies and in immune cells.

Methods: The authors evaluated the expression of IL-13R alpha 1 (IL-13Rα1, an IL-13R subtype) by immunohistochemistry in tissue microarrays of 1213 invasive breast cancer (IBC) samples to determine the prognostic value of IL-13Rα1 expression.

Results: High IL-13Rα1 expression was observed in 619 (51%) cases and was found to be associated with an older (≥50 years) age (p = 0.022), lymph node metastasis (p = 0.015), ductal and micropapillary histologic subtypes (p < 0.001), lymphovascular invasion (p = 0.012), HER2 positivity (p < 0.001), and a high (>20%) Ki-67 index (p = 0.039). No significant correlation was found between IL-13Rα1 expression and clinicopathological variables, including tumor size, histological grade, hormone receptor expressions, and tumor-infiltrating lymphocyte levels. Patients with high IL-13Rα1 expression showed poorer overall survival (p = 0.044) and disease-free survival (DFS, p = 0.001) than those with low/negative expression. Subgroup analysis revealed an association between IL-13Rα1 expression and survival for HER2-negative, but not for HER2-positive tumors. Multivariate analysis showed high IL-13Rα1 expression was an independent negative prognostic factor of DFS (p = 0.019).

Conclusions: The results of this study suggest the IL-13 and IL-13Rα1 interaction promotes cancer cell growth and metastasis, and IL-13Rα1 expression is a potential prognostic marker in IBC.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / surgery
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / secondary*
  • Carcinoma, Ductal, Breast / surgery
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / secondary*
  • Carcinoma, Lobular / surgery
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Interleukin-13 Receptor alpha1 Subunit / metabolism*
  • Lymphatic Metastasis
  • Mastectomy
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology*
  • Neoplasm Recurrence, Local / surgery
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Survival Rate
  • Tissue Array Analysis
  • Young Adult

Substances

  • Biomarkers, Tumor
  • IL13RA1 protein, human
  • Interleukin-13 Receptor alpha1 Subunit
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2