TY - JOUR
T1 - HER2 gene mutations in non-small cell lung carcinomas
T2 - Concurrence with her2 gene amplification and her2 protein expression and phosphorylation
AU - Suzuki, Mikiko
AU - Shiraishi, Kouya
AU - Yoshida, Akihiko
AU - Shimada, Yoko
AU - Suzuki, Kenji
AU - Asamura, Hisao
AU - Furuta, Koh
AU - Kohno, Takashi
AU - Tsuta, Koji
N1 - Funding Information:
We thank Sachiko Miura, Shoichi Harada, and Susumu Wakai for their excellent technical assistance. This work was supported in part by the National Cancer Center Research and Development Fund (26-A-13), and (24-A-1), and Grant-in-Aid for Scientific Research (C) Grant Number 25460446 , and the Advanced Research for Medical Products Mining Program of the National Institute of Biomedical Innovation (NIBIO). The National Cancer Center Biobank is supported by the National Cancer Center Development Fund (Japan).
Publisher Copyright:
© 2014 Elsevier Ireland Ltd.
PY - 2015
Y1 - 2015
N2 - Background: Dysregulation of HER2 signaling pathways results in tumor progression in several types of carcinomas. The aim of the current study is to identify clinicopathological characteristics of HER2-mutated non-small cell lung carcinomas (NSCLCs) in conjunction with HER2 protein expression, gene amplification, and phosphorylation. Patients and methods: We investigated 1275 patients including 1055 adenocarcinomas (ADCs), 146 squamous cell carcinomas, 2 large cell carcinomas, 8 sarcomatoid carcinomas, and 64 adenosquamous carcinomas. High-resolution melting analysis of HER2 hot spot inflame deletion mutations, chromogenic in situ hybridization for HER2 amplification, and immunostaining of wild-type and phosphorylated HER2 was performed. Results: HER2 mutations were detected in 46 (3.6%) of the NSCLCs, with mutations only present in the ADC. When analyzing ADC cases alone, the incidence of HER2 mutation was increased to 4.3%. All HER2-mutated tumors were negative for other driver gene alterations. HER2 mutation status correlated with never-smoker status and patients with smaller tumor size. HER2 amplifications were also identified in approximately half of the tumors with HER2 mutations. The overall survival rate was not significantly different between patients without and with HER2 mutations. When analyzing only invasive ADCs, HER2 mutation status was an independent factor for an unfavorable outcome. Amongst the 46 patients harboring HER2 mutations, univariate and multivariate analysis revealed that HER2 amplification was an unfavorable prognostic factor, while HER2 phosphorylation was a favorable prognostic factor. Conclusions: HER2 mutations were observed in 3.6% of NSCLCs, particularly in younger patients, those with no history of smoking, and those with small tumors. Amongst the patients with HER2 mutations, HER2 amplification and phosphorylation were independent prognostic factors.
AB - Background: Dysregulation of HER2 signaling pathways results in tumor progression in several types of carcinomas. The aim of the current study is to identify clinicopathological characteristics of HER2-mutated non-small cell lung carcinomas (NSCLCs) in conjunction with HER2 protein expression, gene amplification, and phosphorylation. Patients and methods: We investigated 1275 patients including 1055 adenocarcinomas (ADCs), 146 squamous cell carcinomas, 2 large cell carcinomas, 8 sarcomatoid carcinomas, and 64 adenosquamous carcinomas. High-resolution melting analysis of HER2 hot spot inflame deletion mutations, chromogenic in situ hybridization for HER2 amplification, and immunostaining of wild-type and phosphorylated HER2 was performed. Results: HER2 mutations were detected in 46 (3.6%) of the NSCLCs, with mutations only present in the ADC. When analyzing ADC cases alone, the incidence of HER2 mutation was increased to 4.3%. All HER2-mutated tumors were negative for other driver gene alterations. HER2 mutation status correlated with never-smoker status and patients with smaller tumor size. HER2 amplifications were also identified in approximately half of the tumors with HER2 mutations. The overall survival rate was not significantly different between patients without and with HER2 mutations. When analyzing only invasive ADCs, HER2 mutation status was an independent factor for an unfavorable outcome. Amongst the 46 patients harboring HER2 mutations, univariate and multivariate analysis revealed that HER2 amplification was an unfavorable prognostic factor, while HER2 phosphorylation was a favorable prognostic factor. Conclusions: HER2 mutations were observed in 3.6% of NSCLCs, particularly in younger patients, those with no history of smoking, and those with small tumors. Amongst the patients with HER2 mutations, HER2 amplification and phosphorylation were independent prognostic factors.
KW - Adenocarcinoma
KW - HER2 amplification
KW - HER2 mutation
KW - HER2 phosphorylation
KW - HER2 protein expression
KW - Lung
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U2 - 10.1016/j.lungcan.2014.10.014
DO - 10.1016/j.lungcan.2014.10.014
M3 - Article
C2 - 25468202
AN - SCOPUS:84922262212
SN - 0169-5002
VL - 87
SP - 14
EP - 22
JO - Lung Cancer
JF - Lung Cancer
IS - 1
ER -
