Relevance of p185 HER-2/neu oncoprotein quantification in human primary breast carcinoma

The c-erbB-2 proto-oncogene encodes a transmembrane protein tyrosine kinase receptor of 185 kDa (p185) and has been associated with several types of h uman cancers. In human breast cancer, overexpression of p185 occurs in 15-3 0% of cases, correlates with poor prognostic factors and characterizes brea st cancers with a more aggressive behavior. Overexpression of p185 is usual ly associated with c-erbB-2 amplification, though it may occur independentl y and thus define subpopulations of breast cancers which might be of clinic al interest. p185 expression is usually detected by immunohistochemistry (I HC) and few studies have been carried out to evaluate the p185 content of b reast cancers with an ELISA technique. In this context, we showed, in 106 b reast cancer samples, that p185 was expressed at high levels in 13.2%, inte rmediate levels in 55.7% and negative ones in 31.1% of cases. All p185 posi tive samples showed a c-erbB-2 oncogene amplification while none of the p18 5 negative samples and only 4% of p185 imtermediate samples had an amplific ation of c-erbB-2. p185 expression is significantly correlated with the neg ativity of estrogen and progestrone receptors, with high levels of cathepsi n D and in some conditions with axillary nodal involvement. Thus, using the p185 ELISA assay, the c-erbB-2 status of breast cancers can be defined and moreover a subset can be discriminated which is characterized by intermedi ate levels of p185 and absence of c-erbB-2 amplification. The quantitative approach towards p185 in breast cancers affords the possibility of identify ing more appropriately patients with high or low risk and thus permits adap tation of therapeutic regimens.