Immunohistochemical assay (IHC) to study C-erbB-2 status of breast cancer using monoclonal antibody CIBCgp185

The C-erbB-2 proto-oncogene encodes a 185KD glycoprotein with tyrosine kinase activity. Overexpression of this gene either due to gene amplification and/or increased transcription has been observed in a variety of cancers and has been associated with more aggressive disease and a poor clinical prognosis in 20-30% of patients with breast cancer. Besides several prognostic factors like tumor size, histologic grade, steroid hormone receptor status, DNA ploidy, lymph node status etc which are significant in the management of breast cancer, C-erbB-2 status might also serve as an additional parameter. Immunohistochemistry is the most widely used method to study the expression of C-erbB-2 in breast cancer. The very low levels of expression of C-erbB-2 by normal tissues makes this receptor, a potential target for diagnosis and therapy with monoclonal antibodies raised against its extracellular domain. One such monoclonal antibody designated as CIBCgp185 of IgG2a isotype has been generated in our laboratory and extensively characterized. In the present study, an indirect immunohistochemical assay was carried out on frozen tumor tissue sections of 127 malignant breast tumor specimens of various histological types using monoclonal antibody CIBCgp185, which revealed intense staining of tumor cell membrane in 32 specimens, indicating overexpression of C-erbB-2. In the case of 53 benign breast tissues and 24 normal breast tissues studied, this MAb did not exhibit any reactivity. These results suggest that MAb CIBCgp185 might prove useful to identify tumors with overexpression of C-erbB-2 which are often associated with poor prognosis and early recurrence and might have future therapeutic application in the treatment of these cancers.