Mutation analysis of the EGFR pathway genes, EGFR, RAS, PIK3CA, BRAF, and AKT1, in salivary gland adenoid cystic carcinoma

// Kosuke Saida 1, 2, * , Takayuki Murase 1, * , Mayuko Ito 1 , Kana Fujii 1 , Hisashi Takino 1 , Ayako Masaki 1 , Daisuke Kawakita 3 , Kei Ijichi 3 , Yuichiro Tada 4 , Kimihide Kusafuka 5 , Yoshiyuki Iida 6 , Tetsuro Onitsuka 6 , Yasushi Yatabe 7 , Nobuhiro Hanai 8 , Yasuhisa Hasegawa 8 , Hitomi Shinomiya 9 , Ken-Ichi Nibu 9 , Kazuo Shimozato 2 and Hiroshi Inagaki 1 1 Department of Pathology and Molecular Diagnostics, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan 2 Department of Maxillofacial Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, Japan 3 Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan 4 Department of Head and Neck Oncology and Surgery, International University of Health and Welfare Mita Hospital, Tokyo, Japan 5 Pathology Division, Shizuoka Cancer Center, Nagaizumi, Shizuoka, Japan 6 Department of Head and Neck Surgery, Shizuoka Cancer Center, Nagaizumi, Shizuoka, Japan 7 Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan 8 Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan 9 Department of Otolaryngology-Head and Neck Surgery, Kobe University Graduate School of Medicine, Kobe, Japan * These authors contributed equally to this work Correspondence to: Hiroshi Inagaki, email: hinagaki@med.nagoya-cu.ac.jp Keywords: adenoid cystic carcinoma; salivary gland; EGFR pathway mutations; RAS mutations; SNaPshot assay Received: June 16, 2017      Accepted: February 24, 2018     Published: March 30, 2018 ABSTRACT Adenoid cystic carcinoma (AdCC), one of the most common salivary gland carcinomas, usually has a fatal outcome. Epidermal growth factor receptor (EGFR) pathway gene mutations are important in predicting a patient’s prognosis and estimating the efficacy of molecular therapy targeting the EGFR pathway. In this study of salivary gland AdCC (SAdCC), we looked for gene mutations in EGFR, RAS family ( KRAS, HRAS, and NRAS ), PIK3CA, BRAF, and AKT1 , using a highly sensitive single-base extension multiplex assay, SNaPshot. Out of 70 cases, EGFR pathway missense mutations were found in 13 (18.6%): RAS mutations in 10 (14.3%), EGFR in one (1.4%), and PIK3CA in 5 (7.1%). None of the cases showed an EGFR deletion by direct sequencing. Concurrent gene mutations were found in three cases (4.3%). EGFR pathway mutations were significantly associated with a shorter disease-free ( p = 0.011) and overall survival ( p = 0.049) and RAS mutations were as well; ( p = 0.010) and ( p = 0.024), respectively. The gene fusion status as determined by a FISH assay had no significant association with mutations of the genes involved in the EGFR pathway. In conclusion, EGFR pathway mutations, especially RAS mutations, may be frequent in SAdCC, and associated with a poor prognosis for the patient.