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

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Issan Yee San TamMaria P Wong

Abstract

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. 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). 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 2...Continue Reading

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