HER2 gene mutations in non-small cell lung carcinomas: Concurrence with her2 gene amplification and her2 protein expression and phosphorylation

Mikiko Suzuki, Kouya Shiraishi, Akihiko Yoshida, Yoko Shimada, Kenji Suzuki, Hisao Asamura, Koh Furuta, Takashi Kohno, Koji Tsuta

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)14-22
Number of pages9
JournalLung Cancer
Volume87
Issue number1
DOIs
Publication statusPublished - 2015
Externally publishedYes

Fingerprint

erbB-2 Genes
Gene Amplification
Non-Small Cell Lung Carcinoma
Phosphorylation
Mutation
Proteins
Adenocarcinoma
Neoplasms
Adenosquamous Carcinoma
Carcinoma
Large Cell Carcinoma
Sequence Deletion
Freezing
In Situ Hybridization
Squamous Cell Carcinoma
Multivariate Analysis
Survival Rate
Smoking

Keywords

  • Adenocarcinoma
  • HER2 amplification
  • HER2 mutation
  • HER2 phosphorylation
  • HER2 protein expression
  • Lung

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

HER2 gene mutations in non-small cell lung carcinomas : Concurrence with her2 gene amplification and her2 protein expression and phosphorylation. / Suzuki, Mikiko; Shiraishi, Kouya; Yoshida, Akihiko; Shimada, Yoko; Suzuki, Kenji; Asamura, Hisao; Furuta, Koh; Kohno, Takashi; Tsuta, Koji.

In: Lung Cancer, Vol. 87, No. 1, 2015, p. 14-22.

Research output: Contribution to journalArticle

Suzuki, Mikiko ; Shiraishi, Kouya ; Yoshida, Akihiko ; Shimada, Yoko ; Suzuki, Kenji ; Asamura, Hisao ; Furuta, Koh ; Kohno, Takashi ; Tsuta, Koji. / HER2 gene mutations in non-small cell lung carcinomas : Concurrence with her2 gene amplification and her2 protein expression and phosphorylation. In: Lung Cancer. 2015 ; Vol. 87, No. 1. pp. 14-22.
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abstract = "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.",
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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

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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