• Jae Seok Lee, Hye Ryun Kim, Chang Young Lee, Mihwa Shin, and Hyo Sup Shim.
• Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
• Ann. Surg. Oncol. 2013 Sep 1; 20 (9): 3015-22.

BackgroundGene 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.MethodsWe 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.ResultsEGFR 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).ConclusionsEGFR 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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