Clinicopathologic characteristics and prognostic significance of EGFR and p53 mutations in surgically resected lung adenocarcinomas ≤2 cm in maximal dimension

J Surg Oncol. 2014 Aug;110(2):99-106. doi: 10.1002/jso.23628. Epub 2014 Apr 30.

Abstract

Background and objectives: Small lung adenocarcinomas are detected more frequently than in the past. However, the clinicopathologic characteristics and prognostic significance of EGFR/p53 mutations in these tumors remains unclear.

Methods: We evaluated the correlation of EGFR/p53 mutations with clinicopathologic characteristics and tumor relapse in 172 surgically resected lung adenocarcinomas ≤2 cm in maximal dimension. EGFR/p53 mutational analysis was performed on DNA extracted from paraffin-embedded tumors.

Results: EGFR and p53 mutations were identified in 104 (60.5%) and 36 (20.9%) small adenocarcinomas, respectively. EGFR/p53 mutations were associated with tumor size >1 cm, whereas p53 mutations were frequently observed in moderately differentiated tumors. Disease-free survival analysis showed that p53 mutation, presence of visceral pleural surface invasion, elevated preoperative serum carcinoembryonic antigen, and moderate histologic differentiation were significantly correlated with tumor relapse in patients with stage I disease. The 5-year survival rate was higher in relapsed patients with EGFR-mutated tumors who were treated with tyrosine kinase inhibitor (TKI) than in those who were not treated with TKI.

Conclusions: p53 mutation was significantly correlated with tumor progression, and our findings may provide a rationale for the selective use of adjuvant chemotherapy in stage IB patients with p53 mutations. EGFR mutation was a predictor of EGFR TKI response in relapsed patients.

Keywords: epidermal growth factor receptor; lung adenocarcinoma; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / genetics*
  • DNA Mutational Analysis
  • DNA, Neoplasm
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Genes, erbB-1*
  • Genes, p53*
  • Genetic Markers
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Staging
  • Pneumonectomy
  • Prognosis
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Survival Analysis
  • Tumor Burden

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • DNA, Neoplasm
  • Enzyme Inhibitors
  • Genetic Markers
  • Protein-Tyrosine Kinases