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Erschienen in: Annals of Surgical Oncology 4/2014

01.12.2014 | Translational Research and Biomarkers

Prevalence, Clinicopathologic Characteristics, and Molecular Associations of EGFR Exon 20 Insertion Mutations in East Asian Patients with Lung Adenocarcinoma

verfasst von: Yunjian Pan, MD, Yang Zhang, MD, Yuan Li, MD, Haichuan Hu, MD, Lei Wang, MD, Hang Li, MD, Rui Wang, MD, Ting Ye, MD, Xiaoyang Luo, MD, Yiliang Zhang, MD, Bin Li, MD, Deng Cai, MD, Lei Shen, MD, Yihua Sun, MD, Haiquan Chen, MD

Erschienen in: Annals of Surgical Oncology | Sonderheft 4/2014

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Abstract

Purpose

To define the prevalence, clinicopathologic characteristics and molecular associations of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in East Asian lung adenocarcinoma patients.

Methods

A total of 1,086 lung adenocarcinomas were sequenced for EGFR mutations. EGFR and HER2 copy number variations; total and phosphorylated (p) protein expression of ErbB family members including EGFR, HER2, and HER3; phosphorylated protein expression of downstream signaling molecules including Akt and Erk; and clinicopathologic features in lung adenocarcinomas with EGFR exon 20 insertion mutations were all investigated.

Results

EGFR exon 20 insertion mutations were present in 2.9 % of lung adenocarcinomas and 4.7 % of all the EGFR mutations. Compared to those with classic activating EGFR mutations, lung adenocarcinomas with exon 20 insertion mutations were characterized by significantly younger age at diagnosis (P = 0.032 for exon 20 insertions vs. L858R) and shorter relapse-free survival [P = 0.045 for exon 20 insertions versus (vs) exon 19 deletions]. Molecularly, samples harboring exon 20 insertion mutations had lower expression of phosphorylated (p)-EGFR (P < 0.001) and HER3 (P = 0.016). In addition, higher expression of p-Akt (P = 0.007) and lower expression of p-Erk (P = 0.009) were observed in tumors with exon 20 insertion mutations.

Conclusions

Lung adenocarcinomas with EGFR exon 20 insertion mutations were present in a substantial proportion. This subset showed distinct clinicopathologic features, less dependence on EGFR molecularly, and different pathway activation patterns compared to those with classic EGFR activating mutations.
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Metadaten
Titel
Prevalence, Clinicopathologic Characteristics, and Molecular Associations of EGFR Exon 20 Insertion Mutations in East Asian Patients with Lung Adenocarcinoma
verfasst von
Yunjian Pan, MD
Yang Zhang, MD
Yuan Li, MD
Haichuan Hu, MD
Lei Wang, MD
Hang Li, MD
Rui Wang, MD
Ting Ye, MD
Xiaoyang Luo, MD
Yiliang Zhang, MD
Bin Li, MD
Deng Cai, MD
Lei Shen, MD
Yihua Sun, MD
Haiquan Chen, MD
Publikationsdatum
01.12.2014
Verlag
Springer US
Erschienen in
Annals of Surgical Oncology / Ausgabe Sonderheft 4/2014
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-013-3452-1

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