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. 2013 Sep;20(9):3015-22. doi: 10.1245/s10434-013-2937-2. Epub 2013 Mar 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / mortality
  • Adenocarcinoma, Mucinous / pathology
  • Adenocarcinoma, Mucinous / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Acinar Cell / genetics
  • Carcinoma, Acinar Cell / mortality
  • Carcinoma, Acinar Cell / pathology
  • Carcinoma, Acinar Cell / surgery
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Carcinoma, Papillary / genetics
  • Carcinoma, Papillary / mortality
  • Carcinoma, Papillary / pathology
  • Carcinoma, Papillary / surgery
  • Combined Modality Therapy
  • DNA-Binding Proteins / genetics*
  • ErbB Receptors / genetics*
  • Female
  • Follow-Up Studies
  • Gene Amplification*
  • Humans
  • Immunoenzyme Techniques
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use*
  • Retrospective Studies
  • Survival Rate
  • Transcription Factors

Substances

  • DNA-Binding Proteins
  • Protein Kinase Inhibitors
  • TTF1 protein, human
  • Transcription Factors
  • EGFR protein, human
  • ErbB Receptors