Histopathologg zyxwvutsrqponm 1990. zyxwvutsrqp 17. 24 3-247 c-erbB-2 oncoprotein expression in mammary and extramammary Paget’s disease: an immunohistochemical study zyxw L.KEATINGS, J-SINCLAIR, C. WRIGHT, I.P.CORBETT, C. WATCHORN, C.HENNESSY*, B.ANGUS, T.LENNARD* zyxwvu & C.H.W.HORNE Departments of Pathology and *Surgery, University of Newcastle-upon-Tyne, zyxwv UK Date of submission 5 February 1990 Accepted for publication 2 0 March 1990 KEATINGS L., SINCLAIR J., WRIGHT C.. CORBETT I.P., WATCHORN C., HENNESSY C.. ANGUS B.. LENNARD T. & HORNE C.H.W. (1990) Histopathology 17, 243-247 c-erbB-2 oncoprotein expression in mammary and extramammary Paget’s disease: an immunohistochemical study Over-expression of the c-erbB-2 oncogene occurs in a proportion of human adenocarcinomas and in breast carcinoma is associated with poorer prognosis. Sections of formalin-fixed, paraffin-embedded tumour tissue from 22 patients with mammary and extramammary Paget’s disease have been stained immunohistochemically using a monoclonal antibody (NCL-CB11 ) raised against a synthetic peptide from the C-terminal end of the pre- dicted sequence of the c-erbB-2 protein product. All 12 cases of mammary Paget’s disease showed membrane staining of intra-epidermal cells. indicating c-erbB-2 over-expression. Sections of underlying ductal breast carcinoma were available in nine cases: all nine tumours were c-erbB-2 positive and in eight the in situ component was of comedo or solid type. There was membrane staining of tumour cells in four of the 10 cases of extramammary Paget’s disease: staining intensity was generally weaker than that observed in the cases of mammary disease. The possible implications of these findings for the histogenesis of both mammary and extramammary Paget’s disease are discussed. Keywords: breast, carcinoma, c-erbB-2 oncogene, Paget’s disease Introduction The c-erbB-2 oncogene, a member of the tyrosine kinase oncogene family, encodes a transmembrane protein with structural features of a growth factor receptor, although the putative ligand has not been identified’. Amplification of c-erbB-2 in the mouse fibroblast cell line NIH 3T3 results in cellular transformation’ and ex- pression of activated c-neu oncogene (the rat homologue of c-erbB-2) in transgenic mice is associated with the development of mammary carcinomas’.4. Amplification andfor over-expression of c-erbB-2 has been observed in a variety of human adenocarcin~mas~-~ and, in invasive human breast carcinoma, correlates with poorer prog- Address for correspondence: Dr C.Wright. Department of Pathology. Royal Victoria Infirmary, Queen Victoria Road, Newcastle-upon- Tyne NEI 41.P. LIK. nosis9-I4. Over-expression, determined immunohisto- chemically using antibodies raised against the c-erbB-2 oncoprotein, has also been demonstrated in a high proportion of in situ breast carcinomas, predominantly of comedo or solid type’’.lh. In mammary Paget’s disease the epidermis of the nipple is infiltrated by large malignant cells with pleomorphic, vesicular nuclei. An in situ or invasive carcinoma can almost always be demonstrated in the underlying breast, and mammary Paget’s disease is seen in association with approximately 2% of breast carcinomasI7. Extramammary Paget’s disease, which most commonly affects the anogenital area but may also involve other sites, such as the axillae, presents a similar histological appearanceI8. Gusterson and co-workers noted staining of intra-epidermal tumour cells in five ofsix cases of mammary Paget’s disease’’. This observation 243