Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features.

Published

Journal Article

PURPOSE: This study evaluated the mutational profile of epidermal growth factor receptor (EGFR) and KRAS in non-small cell lung cancers in Hong Kong and determined their relation with smoking history and other clinicopathologic features. EXPERIMENTAL DESIGN: Mutational profile of exons 18 to 21 of EGFR and codons 12, 13, and 61 of KRAS were determined in 215 adenocarcinomas, 15 squamous cell (SCC), and 11 EBV-associated lymphoepithelioma-like carcinomas (LELC). RESULTS: EGFR mutations were prevalent in adenocarcinomas (115 of 215), uncommon in LELC (1 of 11), and not found in SCC (P < 0.001). Among adenocarcinomas, mutations were associated with nonsmokers (83 of 111; P < 0.001), female gender (87 of 131; P < 0.001), and well-differentiated (55 of 86) compared with poorly differentiated (11 of 41) tumors (P < 0.001). Decreasing mutation rates with increasing direct tobacco exposure was observed, with 74.8% (83 of 111) in nonsmokers, 61.1% (11 of 18) in passive, 35.7% (10 of 28) in previous, and 19.0% (11 of 58) in current smokers. There were 53% amino acid substitutions, 43% in-frame deletions, and 4% insertions. Complex patterns with 13% double mutations, including five novel substitutions, were observed. For KRAS, mutations occurred in adenocarcinoma only (21 of 215) and were associated with smokers (11 of 58; P = 0.003), men (14 of 84; P = 0.009) and poorly differentiated (7 of 41) compared with well-differentiated (4 of 86) tumors (P = 0.037). EGFR and KRAS mutations occurred in mutually exclusive tumors. Regression analysis showed smoking history was the significant determinant for both mutations, whereas gender was a confounding factor. CONCLUSION: This study shows EGFR mutations are prevalent in lung adenocarcinoma and suggests that it plays an increasing oncogenic role with decreasing direct tobacco damage.

Full Text

Duke Authors

Cited Authors

  • Tam, IYS; Chung, LP; Suen, WS; Wang, E; Wong, MCM; Ho, KK; Lam, WK; Chiu, SW; Girard, L; Minna, JD; Gazdar, AF; Wong, MP

Published Date

  • March 1, 2006

Published In

Volume / Issue

  • 12 / 5

Start / End Page

  • 1647 - 1653

PubMed ID

  • 16533793

Pubmed Central ID

  • 16533793

International Standard Serial Number (ISSN)

  • 1078-0432

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-05-1981

Language

  • eng

Conference Location

  • United States