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

概要

Aims: Mucoepidermoid carcinoma (MEC) is one of the most common salivary gland carcinomas. Epidermal growth factor receptor (EGFR) signaling 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.
A subset of this carcinoma has been associated with a recurring chromosomal translocation, t(11;19)(q21;p13), and this translocation generates the CRTC1–MAML2 fusion gene. The t(11,15)- associated CRTC3–MAML2 fusion gene has also been detected in some MEC cases. CRTC1/3– MAML2 fusions are specific to MEC and may be associated with favorable 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, 1.0 and 5.9%, 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 (R = –0.912) and the fusions were found in 82% of patients aged less than 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.