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Gefitinib, an EGFR tyrosine kinase inhibitor, is a new therapeutic agent for non-small cell lung cancer (NSCLC). Until recently, several somatic mutations in the EGFR tyrosine kinase domain were identified to predict the clinical response of Gefitinib. These mutations include missense mutations in exon 18 (G719S), exon 21 (L858R, L861Q) and different small deletions in exon 19. It is suggested that adenocarcinoma, especially, the variant of Bronchioloalveolar adenocarcinoma (BAC) of lung is more frequently associated with such mutations. In the present study, we investigate and compare the Gefitinib-sensitizing mutation rate of BAC to other adenocarcinoma and squamous cell carcinoma (SCC) in operatable NSCLC Chinese patients in Hong Kong. Ten BAC, 18 non-BAC adenocarcinoma (ACA), 34 SCC and 10 anaplastic large cell carcinoma (ALC) cases were included. Genomic DNA extracted from paraffin-embedded sections, amplified by polymerase chain reaction (PCR), followed by analysis with conformation sensitive gel electrophoresis (CSGE). The aberrant migration bands on the CSGE were cut and sequenced using ABI 3100 system. Among the 10 BAC cases, include 7 female and 3 male patients, 2 were smoker and 8 were non-smoker. In the 18 non-BAC ACA cases, include 7 female and 11 male patients, 11 were smoker and 7 were non-smoker. All 7 non-smokers were female. The EGFR mutation rate in BAC cases was 40% (4/10) and all were female non-smoker. Mutation rate in non-BAC ACA cases was 28% (5/18), in which 2 cases were female non-smoker. The mutation rate in SCC was 12% (4/34) and ALC was 10% (1/10). The mutation rate in BAC was more frequent than non-BAC ACA, but does not attend statistical significance in this small series. However, mutation rate in BAC is significantly higher than that of SCC and ALC (Chi-square, p=0.028). Our results also suggested that EGFR mutation may be more common in female non-smoker patients. Our observations indicated that Gefitinib-sensitizing EGFR mutation is frequent in adenocarcinoma, especially in Bronchioloalveolar type adenocarcinoma. The results may also suggest that such mutations may be more common in female non-smoker patients. Our results implied that treatment with Gefitinib is beneficial in this subset of Hong Kong Chinese patients with NSCLC. The other forms of NSCLC may also harbor such mutations, but in a lower frequency. Pre-treatment screening for EGFR mutation may be useful in selected patients.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]