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EGFR mRNA is Upregulated, but Somatic Mutations of the Gene are Hardly Found in Renal Cell Carcinoma in Japanese Patients

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Purpose

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.

Conclusion

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.

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Abbreviations

CML:

chronic myelogenous leukemia

EGFR:

epidermal growth factor receptor

HER:

human epidermal growth factor receptor

IDEAL:

Iressa dose evaluation in advanced lung cancer

INTACT:

Iressa NSCLC trial assessing combination treatment

NSCLC:

nonsmall cell lung cancer

PCR:

polymerase chain reaction

RCC:

renal cell carcinoma

RT:

reverse transcription

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Acknowledgment

The present study was supported by Yokoyama Foundation for Clinical Pharmacology, Japan.

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Authors and Affiliations

  1. Department of Hospital Pharmacy, School of Medicine, Kobe University, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Toshiyuki Sakaeda, Tsutomu Nakamura & Katsuhiko Okumura

  2. Division of Clinical Pharmacokinetics, Department of General Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Toshiyuki Sakaeda, Masahi Morioka, Kenji Tokui, Hisato Tanaka & Katsuhiko Okumura

  3. Department of Clinical Evaluation of Pharmacotherapy, Kobe University Graduate School of Medicine, 1-5-6, Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan

    Noboru Okamura, Mariko Yagi & Katsuhiko Okumura

  4. Division of Urology, Department of Organs Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Akinobu Gotoh, Toshiro Shirakawa & Shuji Terao

  5. Department of Clinical Genetics and International Center for Medical Research, School of Medicine, Kobe University, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Akinobu Gotoh, Toshiro Shirakawa & Shuji Terao

  6. Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Yoshihiro Nishimura & Mitsuhiro Yokoyama

Authors
  1. Toshiyuki Sakaeda
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  2. Noboru Okamura
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  3. Akinobu Gotoh
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  4. Toshiro Shirakawa
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  6. Masahi Morioka
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  7. Kenji Tokui
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  8. Hisato Tanaka
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  9. Tsutomu Nakamura
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  10. Mariko Yagi
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  11. Yoshihiro Nishimura
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  12. Mitsuhiro Yokoyama
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  13. Katsuhiko Okumura
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Corresponding author

Correspondence to Katsuhiko Okumura.

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Sakaeda, T., Okamura, N., Gotoh, A. et al. EGFR mRNA is Upregulated, but Somatic Mutations of the Gene are Hardly Found in Renal Cell Carcinoma in Japanese Patients. Pharm Res 22, 1757–1761 (2005). https://doi.org/10.1007/s11095-005-7094-2

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  • DOI: https://doi.org/10.1007/s11095-005-7094-2

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