Summary An antibody, 21 N, raised against a synthetic peptide from the predicted sequence of the c-erbB-2 protein has been used immunocytochemically in a retrospective study of formalin fixed paraffin embedded breast biopsies. Fourteen out of 103 infiltrating ductal carcinomas exhibited positive membrane staining. Fifty-four of these tumours had lymph node involvement of which nine contained stained cells. These were all cases where the primary tumour was positive. In this series there was no correlation between c-erbB-2 overexpression and lymph node status. In five of the positive cases studied there was an associated in situ component which was also positively stained. Ten out of 24 pure intraduct carcinomas showed membrane staining, but none of the 149 benign conditions studied, which included 22 radial scars and 13 cases of atypical ductal proliferation, demonstrated the pattern of staining associated with overexpression. It is concluded that the c-erbB-2 protein is overexpressed in a minority (-14%) of infiltrating ductal carcinomas and only in cells that are cytologically malignant. Overexpression of c-erbB-2 is considered in relation to pathogenesis.

An immunohistochemical study of c-erbB-2 expression was performed on invasive and in situ breast cancer. Strong membrane staining was seen in 16% of the infiltrating ductal carcinomas and 44% of the in situ lesions. c-erbB-2 was overexpressed in ductal rather than lobular tumours. Our results indicate that a small sub-group of breast carcinomas are associated with over-expression of this oncogene which may define an important subgroup of in situ and infiltrating ductal carcinomas.

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With the breast carcinoma cell line BT 474 used as a source of antigen, four rat monoclonal antibodies (MAbs) (3 IgG2a and I IgA) have been prepared against the external domain of the product of the c-erbB-2 proto-oncogene. All 4 antibodies stain frozen sections of tissues that over-express the product of the c-erbB-2 proto-oncogene, and competitive binding assays showed that the antibodies recognized 2 non-overlapping epitopes. Representative antibodies from the two groups (ICR12 and 13) were shown to specifically immunoprecipitate a 190 kDa protein from 35S-methionine-labelled breast carcinoma cells where the c-erbB-2 is amplified (BT 474 and MDA-MB 361). Two of the antibodies (ICR12 and ICR17) bind to the denatured antigen in Western blots and ICR12 stains formolsaline-fixed sections of breast carcinoma tissue that over-expresses the product of the c-erbB-2 proto-oncogene. These antibodies should be useful not only for immunocytochemical diagnoses but also for radio-immunoscintigraphic and therapeutic applications.