Activation of the EGFR/ERK pathway in high-grade mucoepidermoid carcinomas of the salivary glands

Br J Cancer. 2010 Aug 10;103(4):510-6. doi: 10.1038/sj.bjc.6605788. Epub 2010 Jul 27.

Abstract

Background: Mucoepidermoid carcinoma (MEC) shows differences in biological behaviour depending mainly on its histological grade. High-grade tumours usually have an aggressive biological course and they require additional oncological treatment after surgery.

Methods: In a series of 43 MECs of the salivary glands, we studied the epidermal growth factor receptor (EGFR) gene by using dual-colour chromogenic in situ hybridisation (CISH). Moreover, we assessed the protein expressions of the EGFR and the activated extracellular signal-regulated kinases (pERK1/2) by using immunohistochemistry. These results were correlated with the histological grade of the tumours and the outcome of the patients.

Results: The CISH study demonstrated a high-EGFR gene copy number, with balanced chromosome 7 polysomy, in 8 out of 11 high-grade MECs (72.7%), whereas 27 low-grade and 15 intermediate-grade tumours had a normal EGFR gene copy number (P<0.001). The EGFR gene gains correlated with disease-free interval (P=0.003) and overall survival of the patients (P=0.019). The EGFR protein expression had a significant correlation with the histological grade of the tumours but not with the outcome of the patients. The pERK1/2 expression correlated with histological grade of tumours (P<0.001), disease-free interval (P=0.004) and overall survival (P=0.001).

Conclusions: The EGFR/ERK pathway is activated in high-grade MECs with aggressive behaviour. Patients with these tumours who require oncological treatment in addition to surgery could benefit from EGFR and mitogen-activated protein kinase pathway inhibitors.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Mucoepidermoid / genetics
  • Carcinoma, Mucoepidermoid / metabolism*
  • Carcinoma, Mucoepidermoid / pathology
  • Carcinoma, Mucoepidermoid / therapy
  • Child
  • Child, Preschool
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Salivary Gland Neoplasms / genetics
  • Salivary Gland Neoplasms / metabolism*
  • Salivary Gland Neoplasms / pathology
  • Salivary Gland Neoplasms / therapy
  • Signal Transduction
  • Young Adult

Substances

  • Biomarkers, Tumor
  • ErbB Receptors
  • Extracellular Signal-Regulated MAP Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3