Distinct Epidermal Growth Factor Receptor and KRAS Mutation Patterns in Non–Small Cell Lung Cancer Patients with Different Tobacco Exposure and Clinicopathologic Features

作者：Issan Yee San Tam, Lap-Ping Chung, Wai Sing Suen, Elaine Wang, May Chun Mei Wong, Kok Keung Ho, Wah Kit Lam, Shui Wah Chiu, Luc Girard, John Dorrance Minna, Adi F. Gazdar, Maria Pik Wong · 发表于：Clinical Cancer Research · 年份：2006 · DOI：10.1158/1078-0432.ccr-05-1981 · 被引用次数：404 · 研究领域：Lung Cancer Treatments and Mutations、Lung Cancer Diagnosis and Treatment、HER2/EGFR in Cancer Research

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 occu...