Expression of amphiregulin in mucoepidermoid carcinoma of the major salivary glands: a molecular and clinicopathological study

Hum Pathol. 2016 Nov:57:37-44. doi: 10.1016/j.humpath.2016.06.016. Epub 2016 Jul 5.

Abstract

In mucoepidermoid carcinoma (MEC), CRTC1-MAML2 fusion indicates a favorable prognosis. Amphiregulin (AREG), an epidermal growth factor receptor (EGFR) ligand, has been shown to be a downstream target of CRTC1-MAML2 fusion, and to play a role in tumor growth and survival in CRTC1-MAML2-positive MEC cell lines. The aim of this study was to characterize the AREG and EGFR expression in the fusion-positive and fusion-negative MEC of the major salivary gland. The AREG and EGFR expression were studied by immunochemistry in 33 MEC cases of the major salivary glands. CRTC1-MAML2 fusion was tested by reverse-transcription polymerase chain reaction (23 CRTC1-MAML2 fusion-positive, 10 fusion-negative). Of 23 fusion-positive cases, AREG and EGFR overexpression were detected in 17 (73.9%) and 14 (60.9%) cases, respectively. Of 10 fusion-negative cases, AREG and EGFR overexpression were detected in 1 (10%) and 3 (30.0%) cases, respectively. There was a positive correlation between CRTC1-MAML2 fusion and AREG overexpression (P < .01), but not between CRTC1-MAML2 fusion and EGFR overexpression. The AREG overexpression was associated with a longer disease-free survival of the MEC patients (P = .042), but EGFR overexpression was not. In this study, we showed that AREG overexpression was detected more frequently in the CRTC1-MAML2 fusion-positive tumors than in fusion-negative tumors. Detection of AREG expression may be useful for identifying CRTC1-MAML2-positive MECs and as a marker for favorable prognosis.

Keywords: AREG; CRTC1-MAML2; EGFR; Mucoepidermoid carcinoma; Prognosis.

MeSH terms

  • Aged
  • Amphiregulin / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Biopsy
  • Carcinoma, Mucoepidermoid / genetics
  • Carcinoma, Mucoepidermoid / metabolism*
  • Carcinoma, Mucoepidermoid / pathology
  • Carcinoma, Mucoepidermoid / surgery
  • Cell Line, Tumor
  • DNA-Binding Proteins / genetics
  • Disease-Free Survival
  • ErbB Receptors / metabolism
  • Female
  • Gene Fusion
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics
  • Predictive Value of Tests
  • Reverse Transcriptase Polymerase Chain Reaction
  • Salivary Gland Neoplasms / genetics
  • Salivary Gland Neoplasms / metabolism*
  • Salivary Gland Neoplasms / pathology
  • Salivary Gland Neoplasms / surgery
  • Time Factors
  • Trans-Activators
  • Transcription Factors / genetics
  • Treatment Outcome

Substances

  • AREG protein, human
  • Amphiregulin
  • Biomarkers, Tumor
  • CRTC1 protein, human
  • DNA-Binding Proteins
  • MAML2 protein, human
  • Nuclear Proteins
  • Trans-Activators
  • Transcription Factors
  • EGFR protein, human
  • ErbB Receptors