Specific KRAS amino acid substitutions and EGFR mutations predict site-specific recurrence and metastasis following non-small-cell lung cancer surgery

Br J Cancer. 2016 Jul 26;115(3):346-53. doi: 10.1038/bjc.2016.182. Epub 2016 Jun 23.

Abstract

Background: We aimed to evaluate whether EGFR mutations (mEGFR) and KRAS amino acid substitutions can predict first site of recurrence or metastasis after non-small-cell lung cancer (NSCLC) surgery.

Methods: Data were reviewed from 481 patients who underwent thoracic surgery for NSCLC between 2007 and 2012.

Results: Patients with KRAS G12C developed significantly more bone metastases compared with the remainder of the cohort (59% vs 16%, P<0.0001). This was confirmed in multivariate analysis (MA) (odds ratio (OR): 0.113 (95% confidence interval (CI): 0.055-0.231), P<0.0001). Significantly, more patients with mEGFR developed liver and brain metastases compared with the remainder of the cohort (30% vs 10%, P=0.006; 59% vs 1%, P<0.0001, respectively). These were confirmed in MA (OR: 0.333 (95% CI: 0.095-0.998), P=0.05; OR: 0.032 (95% CI: 0.008-0.135), P<0.0001, respectively). Patients with KRAS G12V developed significantly more pleuro-pericardial metastases compared with the remainder of the cohort (94% vs 12%, P<0.0001). This was confirmed in MA (OR: 0.007 (95% CI: 0.001-0.031), P<0.0001). Wild-type patients developed significantly more lung metastases (35% vs 10%, P<0.0001). This was confirmed in MA (OR: 0.383 (95% CI: 0.193-0.762), P=0.006).

Conclusion: Epidermal growth factor receptor mutation and KRAS amino acid substitutions seem to predict site-specific recurrence and metastasis after NSCLC surgery.

MeSH terms

  • Aged
  • Amino Acid Substitution*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / surgery
  • ErbB Receptors / genetics*
  • Female
  • Genes, ras*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local

Substances

  • ErbB Receptors