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

ERBB2 (HER-2/neu) amplification and/or overexpression are associated with p oor prognosis in node-positive breast carcinoma Its prognostic value in nod e-negative cases and its predictive value for response to chemotherapy rema in controversial. This may be related to the use of molecular methods, whic h are sensitive to dilution of tumor material by normal cells, or the use o f nonstandardized inmunohistochemistry (IHC) procedures, for the determinat ion of the ERBB2 gene status. In addition, new therapeutic approaches that target the cells overexpressing ERBB2 are under development. These perspect ives necessitate a reliable evaluation of the status of ERBB2 in individual tumors before the application of specific therapeutic strategies. Fluoresc ent 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 invasio n both by IHC, using the CB11 monoclonal antibody and a sensitive Auidin Bi otin Complex (ABC) inmunodetection system, and by FISH, using the Oncor Inf orm HER-2/neu (ERBB2) gene amplification detection system as reference tech nique. 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 overexpress ion of the protein (membrane staining) by IHC. Conversely, ERBB2 expression was present in one case without gene amplification. In conclusion, ERBB2 o verexpression detected by IHC is highly correlated to gene amplification de tected by FISH. Thus, under standardized conditions, INC 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 m embrane immunostaining.