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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

  • Thoracic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Acknowledgment

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).

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Authors and Affiliations

  1. Department of Pathology, Yonsei University College of Medicine, Seoul, Korea

    Jae Seok Lee MD, Mihwa Shin BSc & Hyo Sup Shim MD, PhD

  2. Division of Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea

    Hye Ryun Kim MD

  3. Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea

    Chang Young Lee MD

Authors
  1. Jae Seok Lee MD
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  2. Hye Ryun Kim MD
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  3. Chang Young Lee MD
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  4. Mihwa Shin BSc
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  5. Hyo Sup Shim MD, PhD
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Correspondence to Hyo Sup Shim MD, PhD.

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Lee, J.S., Kim, H.R., Lee, C.Y. et al. 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. Ann Surg Oncol 20, 3015–3022 (2013). https://doi.org/10.1245/s10434-013-2937-2

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  • DOI: https://doi.org/10.1245/s10434-013-2937-2

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