Expression and mutational status of treatment-relevant targets and key oncogenes in 123 malignant salivary gland tumours

Ann Oncol. 2013 Oct;24(10):2624-2629. doi: 10.1093/annonc/mdt338. Epub 2013 Aug 8.


Background: Malignant tumours of the salivary glands (MSGT) are rare and pleomorphic entities. Patients with advanced disease may benefit from targeted therapy; however, specific targets for optimising and personalising treatments are yet to be identified.

Design: Immunohistochemistry for C-KIT, EGFR, HER2, MUC1, phospho-mTOR, androgen/estrogens/progesterone receptors and Ki67 was carried out and evaluated in terms of progression-free and overall survival. High throughput molecular screening of key oncogenes was done in 107 patients using routine diagnostic methods and Sequenom technology.

Results: Several therapy leads were identified, including high levels of HER2 and androgen receptors in salivary duct carcinomas, C-KIT in myoepithelial carcinomas and EGFR in mucoepidermoid carcinomas. Recurrent mutations involving downstream elements of the EGFR pathway were found in HRAS, notably in tumours with a myoepithelial component, and in other key oncogenes (KRAS/NRAS/PI3KCA/BRAF/MAP2K). On the other hand, <1% of samples had EGFR or HER2 mutations.

Conclusion: Several tumour subtypes overexpressed targets of directed therapies suggesting potential therapy leads. Genotyping results suggest activation downstream of EGFR in 18 of the 107 samples that could be associated with low efficacy of EGFR inhibitors. Other molecules, such as PI3K/MEK or mTOR inhibitors, may have anti-tumour activity in this subgroup. The high mutation rate in HRAS highlights a novel key oncogenic event in MSGT.

Keywords: C-KIT; EGFR; HER2; malignant salivary gland tumours; targeted therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Receptor Antagonists / therapeutic use
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Mucoepidermoid / drug therapy
  • Carcinoma, Mucoepidermoid / genetics*
  • Carcinoma, Mucoepidermoid / metabolism
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / biosynthesis
  • ErbB Receptors / metabolism
  • Female
  • Genotype
  • High-Throughput Screening Assays
  • Humans
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Myoepithelioma / drug therapy
  • Myoepithelioma / genetics*
  • Myoepithelioma / metabolism
  • Oncogenes / genetics
  • Proto-Oncogene Proteins c-kit / antagonists & inhibitors
  • Proto-Oncogene Proteins c-kit / biosynthesis
  • Proto-Oncogene Proteins c-kit / metabolism
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / biosynthesis
  • Receptor, ErbB-2 / metabolism
  • Receptors, Androgen / biosynthesis
  • Receptors, Androgen / metabolism
  • Salivary Gland Neoplasms / drug therapy*
  • Salivary Gland Neoplasms / genetics*
  • Salivary Gland Neoplasms / metabolism
  • Survival


  • Androgen Receptor Antagonists
  • Biomarkers, Tumor
  • Receptors, Androgen
  • EGFR protein, human
  • ERBB2 protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins c-kit
  • Receptor, ErbB-2