Strong correlation between results of fluorescent in situ hybridization and immunohistochemistry for the assessment of the ERBB2 (HER-2/neu) gene status in breast carcinoma.

Abstract

ERBB2 (HER-2/neu) amplification and/or overexpression are associated with poor prognosis in node-positive breast carcinoma. Its prognostic value in node-negative cases and its predictive value for response to chemotherapy remain controversial. This may be related to the use of molecular methods, which are sensitive to dilution of tumor material by normal cells, or the use of nonstandardized immunohistochemistry (IHC) procedures, for the determination of the ERBB2 gene status. In addition, new therapeutic approaches that target the cells overexpressing ERBB2 are under development. These perspectives necessitate a reliable evaluation of the status of ERBB2 in individual tumors before the application of specific therapeutic strategies. Fluorescent in situ hybridization (FISH) and IHC allow the evaluation of the ERBB2 status specifically in tumor cells on archival material. We have analyzed a series of 100 invasive ductal breast carcinomas without lymph node invasion both by IHC, using the CB11 monoclonal antibody and a sensitive Auidin Biotin Complex (ABC) immunodetection system, and by FISH, using the Oncor Inform HER-21neu (ERBB2) gene amplification detection system as reference technique. Complete concordance between the results of FISH and IHC was seen in 98% of the cases. ERBB2 amplification (more than four signals per nucleus) was observed in 12 of the 100 cases, and all but one showed an overexpression of the protein (membrane staining) by IHC. Conversely, ERBB2 expression was present in one case without gene amplification. In conclusion, ERBB2 overexpression detected by IHC is highly correlated to gene amplification detected by FISH. Thus, under standardized conditions, IHC is a reliable and economical test to assess the ERBB2 status in tumors. The use of FISH could be limited to the verification of the status of tumors displaying a weak membrane immunostaining.

• Authors: J Couturier, A Vincent-Salomon, A Nicolas, P Beuzeboc, E Mouret, B Zafrani, X Sastre-Garau
• Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (Mod Pathol) Vol. 13 Issue 11 Pg. 1238-43 (Nov 2000) ISSN: 0893-3952 [Print] United States
• PMID: 11106082 (Publication Type: Comparative Study, Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Neoplasm
• Receptor, ErbB-2

Topics

• Breast Neoplasms (genetics, metabolism, pathology)
• Carcinoma, Ductal, Breast (genetics, metabolism, pathology)
• DNA, Neoplasm (analysis)
• Female
• Genes, erbB-2
• Humans
• Immunoenzyme Techniques (methods)
• In Situ Hybridization, Fluorescence (methods)
• Middle Aged
• Receptor, ErbB-2 (metabolism)
• Reproducibility of Results
• Sensitivity and Specificity