EGFR mRNA is upregulated, but somatic mutations of the gene are hardly found in renal cell carcinoma in Japanese patients.
OBJECTIVE
Heterozygous somatic mutations of epidermal growth factor receptor (EGFR) in exons 18, 19, and 21 were recently reported to be associated with response to gefitinib in patients having nonsmall cell lung cancer. Such mutations are more frequently found among Japanese than Europeans. In this work, the frequency of mutations was investigated in renal cell carcinoma (RCC) samples obtained from Japanese subjects to examine the potential of gefitinib as a therapeutic agent for RCC.


METHODS
Nineteen patients with RCC, who gave written informed consent, were enrolled in this study. mRNA expression levels of EGFR were measured in RCC and its adjacent noncancerous renal tissue via the real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. Somatic mutations were determined using genomic DNA extracted from RCC by direct sequencing method.


RESULTS
mRNA expression was confirmed to be about 19 times higher in RCC than in adjacent noncancerous renal tissues, but no such mutations were detected in both.


CONCLUSIONS
Results from this study do not support the validity of further clinical trials on gefitinib for RCC with genotyping even in Japanese patients, although EGFR plays a key role in tumor progression.
Sakaeda
Toshiyuki
T
Department of Hospital Pharmacy, School of Medicine, Kobe University, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Okamura
Noboru
N
Gotoh
Akinobu
A
Shirakawa
Toshiro
T
Terao
Shuji
S
Morioka
Masahi
M
Tokui
Kenji
K
Tanaka
Hisato
H
Nakamura
Tsutomu
T
Yagi
Mariko
M
Nishimura
Yoshihiro
Y
Yokoyama
Mitsuhiro
M
Okumura
Katsuhiko
K
D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D006801:Humans; D007564:Japan; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D012333:RNA, Messenger; D066246:ErbB Receptors