Mutations of the EGFR, K-ras, EML4-ALK, and BRAF genes in resected pathological stage I lung adenocarcinoma

Surg Today. 2016 Sep;46(9):1091-8. doi: 10.1007/s00595-015-1295-z. Epub 2015 Dec 28.

Abstract

Background and purpose: The EGFR, K-ras, EML4-ALK, and BRAF genes are oncogenic drivers of lung adenocarcinoma. We conducted this study to analyze the mutations of these genes in stage I adenocarcinoma.

Methods: The subjects of this retrospective study were 256 patients with resected stage I lung adenocarcinoma. We analyzed mutations of the EGFR, K-ras, and BRAF genes, and the EML4-ALK fusion gene. We also assessed disease-free survival (DFS) to evaluate the prognostic value and overall survival (OS) to evaluate the predictive value of treatment after recurrence.

Results: Mutations of the EGFR, K-ras, EML4-ALK, and BRAF genes were detected in 120 (46.8 %), 14 (5.5 %), 6 (2.3 %), and 2 (0.8 %) of the 256 tumors. Two tumors had double mutations (0.8 %). The incidence of EGFR mutations was significantly higher in women than in men. The EML4-ALK fusion gene was detected only in younger patients. The DFS and OS of the K-ras mutant group were significantly worse than those of the EGFR mutant group, the EML4-ALK fusion gene group, and the wild-type group. Six of the seven patients with the EML4-ALK fusion gene are still alive without recurrent disease.

Conclusions: In patients with stage I adenocarcinoma, mutation of the K-ras gene was a poor prognostic factor for recurrence. The presence of a mutation of the EGFR or EML4-ALK gene was not a prognostic factor.

Keywords: Adenocarcinoma; BRAF; EGFR; EGFR-TKI; EML4–ALK; K-ras; NSCLC.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Anaplastic Lymphoma Kinase
  • Cell Cycle Proteins / genetics*
  • ErbB Receptors
  • Female
  • Genes, erbB-1 / genetics*
  • Genes, ras / genetics*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Male
  • Microtubule-Associated Proteins / genetics*
  • Middle Aged
  • Mutation*
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics*
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Retrospective Studies
  • Serine Endopeptidases / genetics*

Substances

  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • EGFR protein, human
  • ErbB Receptors
  • Receptor Protein-Tyrosine Kinases
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • EML4 protein, human
  • Serine Endopeptidases