Interleukin-33 Expression Indicates a Favorable Prognosis in Malignant Salivary Gland Tumors

Int J Surg Pathol. 2016 Aug;24(5):394-400. doi: 10.1177/1066896916633856. Epub 2016 Feb 23.


The cytokine interleukin-33 (IL-33) is abundantly expressed in epithelial barrier tissues such as salivary glands. Here, we characterized nuclear IL-33 protein expression by immunohistochemistry in benign and malignant salivary gland tumors and associated it with disease outcome. Most benign salivary gland tumors expressed IL-33, and all Warthin's tumors showed strong and consistent IL-33 expression in the basally oriented cells of their bilayered epithelium. In the malignant group of neoplasms, nuclear IL-33 expression was limited to specific tumor entities-for example, to epithelial-myopepithelial carcinomas (n = 9/11), acinic cell carcinomas (n = 13/27), and oncocytic carcinomas (n = 2/2). IL-33 expression in the combined group of malignant salivary gland neoplasms was significantly associated with favorable histological parameters, lack of metastasis, and longer overall survival, compared with IL-33-negative tumors. We conclude that IL-33 expression is a novel prognostic marker for malignant salivary gland tumors with potential use in clinical diagnostics.

Keywords: biomarker; immunohistochemistry; interleukin-33; prognosis; salivary gland; tissue microarray.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Child
  • Female
  • Humans
  • Immunohistochemistry
  • Interleukin-33 / analysis
  • Interleukin-33 / biosynthesis*
  • Male
  • Middle Aged
  • Prognosis
  • Salivary Gland Neoplasms / diagnosis*
  • Salivary Gland Neoplasms / mortality
  • Salivary Gland Neoplasms / pathology
  • Survival Analysis
  • Tissue Array Analysis
  • Young Adult


  • Biomarkers, Tumor
  • IL33 protein, human
  • Interleukin-33