Klin Onkol 2001; 14(5): 157-162.
Summary:
Background: The HER-2/neu proto-oncogene encodes one of the epithelial growth factor receptors in the cell membrane, the functions of which include stimulation of mammary epithelial cell proliferation. In breast carciomas, overexpression has been reported in 10-34% of invasive cancer. Data published to date shows that ERBB2/HER-2 protein overexpression has been caused by gene amplification in 90% of these cases and has been shown to be associated with poor prognosis. Results of both preclinical and clinical studies show that laboratory assessment of ERBB2/HER-2 status can be useful not only as a prognostic factor in breast cancer, but also as a predictive marker for projecting response to different therapy regimens.
Design and subjects: Standardised determination of ERBB2/HER-2 status has become more important. The purpose of this study has been a determination of the validity of different methods for detecting the status of ERBB2/HER-2 oncogene in formalin fixed and paraffin-embedded breast cancer tissues for diagnostic use.
Methods and results: Sixty routinely formalin fixed and paraffin-embedded invasive breast carcinoma tissues were investigated both by fluorescence in situ hybridisation (FISH) using INFORMTM Her-2/neu Gene Detection system (Ventana) and by immunohistochemistry (IHC) using DAKOHercepTestTM and Novocastra monoclonal antibodies (NCL-HER2-356, NCL-HER2-316, NCL-CB11). Amplification was detected in 13.3% of the cases. Overexpression was detected in 13.3-28.3% of the cases depending on the methodology and/or reagent used. Perfect concordance was found between results of FISH and IHC using NCL-HER2-356 as well as between FISH and IHC using NCL-HER2-316 with no antigen retrieval. Nine DAKO-HercepTestTM positive carcinomas (seven 2+, two 3+) were classified as non amplified using FISH.
Conclusions: Our results indicate that high level expression as well as normal ERBB2/HER-2 status can be reliably detected both by IHC and FISH using the standardised methodology. Borderline results, especially 2+ immunopositivity should be interpreted with caution using both methods (IHC and FISH) with standardised methodological approaches. An algorithm of screening and evaluation of ERBB2/HER2 status using both above approaches is suggested.
