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EGFR and TTF-1 Gene Amplification in Surgically Resected Lung Adenocarcinomas: Clinicopathologic Significance and Effect on Response to EGFR-Tyrosine Kinase Inhibitors in Recurred Cases

Authors
 Jae Seok Lee ; Hye Ryun Kim ; Hyo Sup Shim ; Mihwa Shin ; Chang Young Lee 
Citation
 Annals of Surgical Oncology, Vol.20(9) : 3015~3022, 2013 
Journal Title
 Annals of Surgical Oncology 
ISSN
 1068-9265 
Issue Date
2013
Abstract
Background Gene amplifications are implicated in cancer development and progression. In this study we investigated the clinicopathologic characteristics associated with EGFR or TTF-1 amplification in lung adenocarcinomas and its prognostic significance. Methods We analyzed 118 cases of surgically resected primary lung adenocarcinomas. Amplification of the EGFR or TTF-1 gene was evaluated by fluorescence in situ hybridization and correlated with patients’ clinicopathologic features, including disease-free survival (DFS) and overall survival (OS), in all patients and a subset that were TTF-1 positive or had EGFR mutation. Progression-free survival (PFS) also was analyzed among patients with EGFR mutation who had recurred cancer that was treated with EGFR tyrosine kinase inhibitors. Results EGFR or TTF-1 gene amplification was an independent poor prognostic factor for DFS in all patients (p = 0.001), in patients with TTF-1 positivity (p = 0.010), and in patients with EGFR mutation (p < 0.001) and for OS in patients with TTF-1 positivity (p = 0.021) and patients with EGFR mutation (p < 0.001). Patients with TTF-1 amplification had a shorter PFS following EGFR TKI treatment (p = 0.040). Conclusions EGFR or TTF-1 gene amplification was a predictive factor for poor prognosis in terms of DFS and OS, especially in patients with TTF-1 positivity or EGFR mutation. Our results also suggested that TTF-1 amplification might be a predictive marker of poor response to EGFR-TKI therapy in patients with recurrent tumor after surgical resection.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/87648
DOI
10.1245/s10434-013-2937-2
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Yonsei Biomedical Research Center
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
1. 연구논문 > 1. College of Medicine > Dept. of Pathology
1. 연구논문 > 1. College of Medicine > Dept. of Thoracic & Cardiovascular Surgery
Yonsei Authors
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Link
 http://link.springer.com/article/10.1245%2Fs10434-013-2937-2
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