Clinicopathological significance of EGFR pathway gene mutations and CRTC1/3-MAML2 fusions in salivary gland mucoepidermoid carcinoma

Histopathology. 2020 Jun;76(7):1013-1022. doi: 10.1111/his.14100. Epub 2020 May 15.

Abstract

Aims: Mucoepidermoid carcinoma (MEC) is one of the most common salivary gland carcinomas. Epidermal growth factor receptor (EGFR) signalling pathway gene mutations are important in predicting a patient's prognosis, selecting molecularly targeted drugs and estimating the efficacy of a molecular therapy. However, their significance in MEC have been poorly clarified. CRTC1/3-MAML2 fusions are specific to MEC and may be associated with favourable characteristics in these patients.

Methods and results: We looked for CRTC1/3-MAML2 fusions and gene alterations in the EGFR, RAS family (KRAS, HRAS and NRAS), PIK3CA, BRAF and AKT1 in 101 MEC cases. We also examined mutations in TP53. CRTC1/3-MAML2 fusions were found in 62.4% of the cases. KRAS, HRAS and PIK3CA mutations were detected in 6.9%, 2.0% and 6.9%, respectively, but other EGFR pathway genes were not mutated. In total, gene mutations (RAS/PIK3CA) in the EGFR pathway were detected in 14.9% of the cases. TP53 mutations were found in 20.8%. CRTC1/3-MAML2 fusions were associated with a better prognosis and RAS/PIK3CA mutations a worse prognosis of the patients, respectively, and both were selected as independent prognostic factors for the overall survival of the patients. TP53 mutations had no prognostic impact. CRTC1/3-MAML2 fusion-positive rates were inversely associated with the patients' age and the fusions were found in 82% of patients aged < 30 years.

Conclusions: RAS/PIK3CA mutations were frequently detected, and may be a biomarker for a poorer prognosis in MEC patients. CTRC1/3-MAML2 fusions were positive in most of the young MEC patients.

Keywords: CTRC1/3-MAML2 fusions; EGFR pathway; patient age; prognosis; salivary gland mucoepidermoid carcinoma.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Mucoepidermoid / genetics*
  • Carcinoma, Mucoepidermoid / pathology*
  • Child
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Oncogene Fusion / genetics
  • Oncogene Proteins, Fusion / genetics
  • Salivary Gland Neoplasms / genetics*
  • Salivary Gland Neoplasms / pathology*
  • Trans-Activators / genetics
  • Transcription Factors / genetics
  • Young Adult

Substances

  • Biomarkers, Tumor
  • CRTC1 protein, human
  • CRTC3 protein, human
  • MAML2 protein, human
  • Oncogene Proteins, Fusion
  • Trans-Activators
  • Transcription Factors
  • EGFR protein, human
  • ErbB Receptors