High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan.
OBJECTIVE
Epidermal growth factor receptor (EGFR) mutations related to gefitinib responsiveness in non-small cell lung cancer have been found recently. Detection of EGFR mutations has become an important issue for therapeutic decision-making in non-small cell lung cancer.


METHODS
Mutational analysis of the kinase domain of EGFR coding sequence was done on 101 fresh frozen tumor tissues from patients without prior gefitinib treatment and 16 paraffin-embedded tumor tissues from patients treated with gefitinib. Detection of phosphorylated EGFR by immunoblot was also done on frozen tumor tissues.


RESULTS
The 101 non-small cell lung cancer tumor specimens include 69 adenocarcinomas, 24 squamous cell carcinomas, and 8 other types of non-small cell lung cancers. Mutation(s) in the kinase domain (exon 18 to exon 21) of the EGFR gene were identified in 39 patients. All of the mutations occurred in adenocarcinoma, except one that was in an adenosquamous carcinoma. The mutation rate in adenocarcinoma was 55% (38 of 69). For the 16 patients treated with gefitinib, 7 of the 9 responders had EGFR mutations, and only 1 of the 7 nonresponders had mutations, which included a nonsense mutation. The mutations seem to be complex in that altogether 23 different mutations were observed, and 9 tumors carried 2 mutations.


CONCLUSIONS
Data from our study would predict a higher gefitinib response rate in lung adenocarcinoma patients in Chinese and, possibly, other East Asian populations. The tight association with adenocarcinoma and the high frequency of mutations raise the possibility that EGFR mutations play an important role in the tumorigenesis of adenocarcinoma of lung, especially in East Asians.
Huang
Shiu-Feng
SF
Division of Molecular and Genomic Medicine, National Health Research Institutes, Taipei, Taiwan.
Liu
Hui-Ping
HP
Li
Ling-Hui
LH
Ku
Yuan-Chieh
YC
Fu
Yu-Ning
YN
Tsai
Hsien-Yu
HY
Chen
Ya-Ting
YT
Lin
Yung-Feng
YF
Chang
Wen-Cheng
WC
Kuo
Han-Pin
HP
Wu
Yi-Cheng
YC
Chen
Yi-Rong
YR
Tsai
Shih-Feng
SF
D000230:Adenocarcinoma / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D018196:Carcinoma, Adenosquamous / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D000077156:Gefitinib; D006801:Humans; D015151:Immunoblotting; D008175:Lung Neoplasms / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010766:Phosphorylation / Q000187:drug effects; D011799:Quinazolines / Q000627:therapeutic use*; D012689:Sequence Homology, Nucleic Acid; D013624:Taiwan / Q000453:epidemiology
D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib