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

2013-03-02 13:57:11

Annals of Surgical Oncology; 2013 Sep; 20(9):3015-22

Jae Seok Lee, Hye Ryun Kim, Chang Young Lee, Mihwa Shin, Hyo Sup Shim



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.


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.


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).


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.

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