Premium
Clinicopathological significance of EGFR pathway gene mutations and CRTC1/3–MAML2 fusions in salivary gland mucoepidermoid carcinoma
Author(s) -
Morita Maki,
Murase Takayuki,
Okumura Yoshihide,
Ueda Kaori,
Sakamoto Yuma,
Masaki Ayako,
Kawakita Daisuke,
Tada Yuichiro,
Nibu KenIchi,
Shibuya Yasuyuki,
Inagaki Hiroshi
Publication year - 2020
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.14100
Subject(s) - hras , kras , neuroblastoma ras viral oncogene homolog , mucoepidermoid carcinoma , cancer research , fusion gene , gene , biomarker , medicine , oncology , epidermal growth factor receptor , biology , mutation , cancer , carcinoma , genetics
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.