Clonality status of multifocal lung adenocarcinomas based on the mutation patterns of EGFR and K-ras

Lung Cancer. 2012 Mar;75(3):313-20. doi: 10.1016/j.lungcan.2011.08.007. Epub 2011 Dec 29.

Abstract

Purpose: The purpose of this study is to clarify the clonality status of multifocal lung adenocarcinomas based on the mutation patterns of epidermal growth factor receptor (EGFR) and K-ras.

Methods: We analyzed 82 multifocal lung adenocarcinomas from 36 patients who underwent surgical resection. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue and analyzed for EGFR and K-ras mutations. We determined the clonality status of multifocal lung adenocarcinomas based on the mutation patterns of EGFR and K-ras. The actuarial survival time was estimated and the prognostic factors were evaluated for 31 patients with synchronous multifocal lung adenocarcinomas.

Results: EGFR and K-ras mutations were detected in 36 (44%) and 19 (23%) of the 82 tumors, respectively. EGFR mutations had occurred randomly in 20 (91%) of the 22 patients with at least one EGFR mutated tumor. K-ras mutations had occurred randomly in 14 (93%) of the 15 patients with at least one K-ras mutated tumor. Combining the results for the EGFR and K-ras mutation patterns, the clonality status of multifocal lung adenocarcinomas could be determined in 30 (83%) of the 36 patients. No statistically significant difference in the actuarial survival of the patient subgroups stratified according to the clonality status, which was based on the presence of EGFR and K-ras mutations, was observed.

Conclusions: Both EGFR and K-ras mutations frequently occur randomly in multifocal lung adenocarcinomas. Combined mutation pattern analyses of EGFR and K-ras may be useful for making decisions regarding treatment strategies for patients with multifocal lung adenocarcinomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology*
  • Adenocarcinoma / surgery
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • ErbB Receptors / genetics*
  • Female
  • Genes, ras*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasms, Multiple Primary / genetics
  • Neoplasms, Multiple Primary / mortality
  • Neoplasms, Multiple Primary / pathology
  • Neoplasms, Multiple Primary / surgery
  • Predictive Value of Tests
  • Survival Rate

Substances

  • EGFR protein, human
  • ErbB Receptors