Yuma Sakamoto
   Department   Kawasaki Medical School  Kawasaki Medical School, Department of Immunology and Molecular Genetics,
   Position   Instructor
Article types 原著
Language English
Peer review Peer reviewed
Title Clinicopathological significance of EGFR pathway gene mutations and CRTC1/3-MAML2 fusions in salivary gland mucoepidermoid carcinoma.
Journal Formal name：Histopathology
Abbreviation：Histopathology
ISSN code：13652559/03090167
Domestic / ForeginForegin
Volume, Issue, Page 76(7),pp.1013-1022
Author and coauthor Maki Morita, Takayuki Murase, Yoshihide Okumura, Kaori Ueda, Yuma Sakamoto, Ayako Masaki, Daisuke Kawakita, Yuichiro Tada, Ken-Ichi Nibu, Yasuyuki Shibuya, Hiroshi Inagaki
Publication date 2020/06
Summary 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.
DOI 10.1111/his.14100
PMID 32129900