Virchows Archiv

, Volume 445, Issue 3, pp 255–262 | Cite as

A proposal for diagnostically meaningful criteria to classify increased epidermal growth factor receptor and c-erbB-2 gene copy numbers in gastric carcinoma, based on correlation of fluorescence in situ hybridization and immunohistochemical measurements

  • Mikihiko Kimura
  • Hitoshi TsudaEmail author
  • Daisaku Morita
  • Takashi Ichikura
  • Sho Ogata
  • Shinsuke Aida
  • Yutaka Yoshizumi
  • Tadaaki Maehara
  • Hidetaka Mochizuki
  • Osamu Matsubara
Original Article


Amplification of the epidermal growth factor receptor (EGFR) and/or c-erbB-2 oncogenes and overexpression of their proteins are detected in 30% of gastric carcinomas, but there are few reports regarding the correlation between gene amplification and protein overexpression. We examined the correlation between amplification of the EGFR and c-erbB-2 genes, detected using fluorescence in situ hybridization, and overexpression of their proteins, detected using immunohistochemistry, in formalin-fixed tissue sections of 54 surgically resected gastric carcinomas. A mean EGFR copy number per nucleus of four or more and an EGFR/chromosome 7 centromere (CEP7) ratio of 1.7 or more were each detected in 4 specimens (7%). The sensitivity and specificity of both criteria for EGFR protein overexpression were 75% and 92%, respectively. A mean c-erbB-2 copy number per nucleus of 7.0 or more and a c-erbB-2/chromosome 17 centromere (CEP17) ratio of 2.0 or more were detected in six (11%) and eight (15%) specimens, respectively. The sensitivity and specificity of the former criterion to c-erbB-2 overexpression were 83% and 98%, respectively, while those of the latter were 63% and 98%. A mean EGFR gene copy number of 4.0 or more and/or an EGFR/CEP7 ratio of 1.7 and a mean c-erbB-2 gene copy number of 7.0 or more and/or a c-erbB-2/CEP17 ratio of 2.0 or more would be useful in defining increased EGFR and c-erbB-2 gene copy numbers, respectively, in gastric carcinomas.


Epidermal growth factor receptor C-erbB-2(HER2) Fluorescence in situ hybridization Immunohistochemistry Gastric carcinoma 



Supported in part by Grants-in-Aid from the Foundation for the Promotion of Cancer Research, Japan, the Chugai Pharmaceutical Co., Japan, the Fujisawa Pharmaceutical Co., Japan, and the Taiho Pharmaceutical Co., Japan, and a Grant-in-Aid to young researchers from the National Defense Medical College, Tokorozawa, Japan.


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Mikihiko Kimura
    • 1
  • Hitoshi Tsuda
    • 1
    Email author
  • Daisaku Morita
    • 1
  • Takashi Ichikura
    • 2
  • Sho Ogata
    • 3
  • Shinsuke Aida
    • 3
  • Yutaka Yoshizumi
    • 4
  • Tadaaki Maehara
    • 4
  • Hidetaka Mochizuki
    • 2
  • Osamu Matsubara
    • 1
  1. 1.Department of Pathology IINational Defense Medical CollegeSaitama Japan
  2. 2.Department of Surgery INational Defense Medical CollegeSaitama Japan
  3. 3.Department of Laboratory MedicineNational Defense Medical CollegeSaitama Japan
  4. 4.Department of Surgery IINational Defense Medical CollegeSaitama Japan

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