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Journal of Molecular Medicine

, Volume 84, Issue 8, pp 671–681 | Cite as

Gene amplification, mutation, and protein expression of EGFR and mutations of ERBB2 in serous ovarian carcinoma

  • Heini Lassus
  • Harri Sihto
  • Arto Leminen
  • Heikki Joensuu
  • Jorma Isola
  • Nina N. Nupponen
  • Ralf Butzow
Original Article

Abstract

EGFR and erbB-2 are targets for specific cancer therapy. The purpose of this study was to examine the frequency and clinicopathological correlations of gene amplification, protein expression, and mutations of EGFR and ERBB2 in serous carcinoma, the most common and aggressive type of ovarian cancer. Tissue microarray constructed of 398 carcinomas was examined by chromogenic in situ hybridization (CISH) and by immunohistochemistry. Cases with amplification of EGFR by CISH were further analyzed by fluorescence in situ hybridization. One hundred ninety-eight samples were analyzed for mutations in exons 18, 19, or 21 of EGFR and in exon 20 of ERBB2 using denaturating high-performance liquid chromatography and direct sequencing. Amplification of EGFR was present in 12% (41/333), low-level gain in 43% (144/333), and protein overexpression in 17% (66/379) of the tumors. Both increased copy number and overexpression of EGFR were associated with high tumor grade, greater patient age, large residual tumor size, high proliferation index, aberrant p53, and poor patient outcome. Furthermore, increased copy number of EGFR was associated with increased copy number of ERBB2. No mutations were identified in EGFR, whereas one tumor had an insertion mutation in exon 20 of ERBB2. Both amplification and protein overexpression of EGFR occur in serous ovarian carcinoma, but EGFR copy number has a stronger prognostic value. This makes EGFR amplification a potentially useful criterion for selecting patients in clinical trials testing the effect of EGFR inhibitors in serous ovarian carcinoma.

Keywords

Cystadenocarcinoma Serous erbB-1 erbB-2 Gene amplification Mutation 

Notes

Acknowledgements

This study is supported by grants from the Cancer Society of Finland, Foundation for the Finnish Cancer Institute, the Academy of Finland, and Helsinki University Central Hospital.

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Heini Lassus
    • 1
    • 2
  • Harri Sihto
    • 3
  • Arto Leminen
    • 5
  • Heikki Joensuu
    • 3
  • Jorma Isola
    • 4
  • Nina N. Nupponen
    • 3
  • Ralf Butzow
    • 1
    • 6
  1. 1.Department of Obstetrics and GynecologyHelsinki University Central HospitalHelsinkiFinland
  2. 2.Department of Obstetrics and GynecologyJorvi HospitalEspooFinland
  3. 3.Laboratory of Molecular Oncology, Department of OncologyHelsinki University Central Hospital, University of Helsinki, BiomedicumHelsinkiFinland
  4. 4.Institute of Medical TechnologyUniversity of TampereTampereFinland
  5. 5.Department of Obstetrics and GynecologyHelsinki University Central HospitalHelsinkiFinland
  6. 6.Department of PathologyUniversity of HelsinkiHelsinki 00014Finland

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