Annals of Surgical Oncology

, Volume 20, Issue 9, pp 3015–3022 | Cite as

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

  • Jae Seok Lee
  • Hye Ryun Kim
  • Chang Young Lee
  • Mihwa Shin
  • Hyo Sup ShimEmail author
Thoracic Oncology



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.


Overall Survival Epidermal Growth Factor Receptor Epidermal Growth Factor Receptor Mutation Anaplastic Lymphoma Kinase Bacterial Artificial Chromosome Clone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (2011-0014077).

Supplementary material

10434_2013_2937_MOESM1_ESM.doc (1.5 mb)
Supplementary material 1 (DOC 1544 kb)


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Copyright information

© Society of Surgical Oncology 2013

Authors and Affiliations

  • Jae Seok Lee
    • 1
  • Hye Ryun Kim
    • 2
  • Chang Young Lee
    • 3
  • Mihwa Shin
    • 1
  • Hyo Sup Shim
    • 1
    Email author
  1. 1.Department of PathologyYonsei University College of MedicineSeoulKorea
  2. 2.Division of Oncology, Department of Internal MedicineYonsei Cancer Center, Yonsei University College of MedicineSeoulKorea
  3. 3.Department of Thoracic and Cardiovascular SurgeryYonsei University College of MedicineSeoulKorea

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