Pharmaceutical Research

, Volume 22, Issue 10, pp 1757–1761

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

  • Toshiyuki Sakaeda
  • Noboru Okamura
  • Akinobu Gotoh
  • Toshiro Shirakawa
  • Shuji Terao
  • Masahi Morioka
  • Kenji Tokui
  • Hisato Tanaka
  • Tsutomu Nakamura
  • Mariko Yagi
  • Yoshihiro Nishimura
  • Mitsuhiro Yokoyama
  • Katsuhiko Okumura
Short Communication

DOI: 10.1007/s11095-005-7094-2

Cite this article as:
Sakaeda, T., Okamura, N., Gotoh, A. et al. Pharm Res (2005) 22: 1757. doi:10.1007/s11095-005-7094-2

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.

Key Words

EGF receptorrenal cell carcinomasomatic mutation

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

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Toshiyuki Sakaeda
    • 1
    • 2
  • Noboru Okamura
    • 3
  • Akinobu Gotoh
    • 4
    • 5
  • Toshiro Shirakawa
    • 4
    • 5
  • Shuji Terao
    • 4
    • 5
  • Masahi Morioka
    • 2
  • Kenji Tokui
    • 2
  • Hisato Tanaka
    • 2
  • Tsutomu Nakamura
    • 1
  • Mariko Yagi
    • 3
  • Yoshihiro Nishimura
    • 6
  • Mitsuhiro Yokoyama
    • 6
  • Katsuhiko Okumura
    • 1
    • 2
    • 3
  1. 1.Department of Hospital Pharmacy, School of MedicineKobe UniversityKobeJapan
  2. 2.Division of Clinical Pharmacokinetics, Department of General Therapeutics, Faculty of MedicineKobe University Graduate School of MedicineKobeJapan
  3. 3.Department of Clinical Evaluation of PharmacotherapyKobe University Graduate School of MedicineKobeJapan
  4. 4.Division of Urology, Department of Organs Therapeutics, Faculty of MedicineKobe University Graduate School of MedicineKobeJapan
  5. 5.Department of Clinical Genetics and International Center for Medical Research, School of MedicineKobe UniversityKobeJapan
  6. 6.Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Faculty of MedicineKobe University Graduate School of MedicineKobeJapan