Abstract
Mammary Paget's disease (MPD) and extramammary Paget's disease (EMPD) are rare neoplasms. The aim of this study was, by the use of immunohistochemistry, to derive further information about the cell(s) of origin, find a diagnostically useful immunohistochemical panel and investigate candidates for possible targeted therapy. Sixty MPD and 23 EMPD cases were studied using antibodies to cytokeratin (CK) 34betaE12, CK8/18, CK7, CK5/6, CK20, gross cyctic disease fluid protein (GCDFP)-15, MUC1-8, epidermal growth factor receptor (EGFR) (HER1), HER3 and HER4. In all MPD cases CK7 and MUC1 were positive. CK8/18 was positive in 59/60 cases. GCDFP-15, MUC2, MUC3, MUC4, MUC7, MUC8 were positive in 29/60, 3/60, 35/47, 4/40, 3/43 and 2/45 cases, respectively. In all EMPD cases CK8/18 and CK7 were positive. MUC1, GCDFP-15, MUC5AC, MUC3, MUC8 and CK20 were positive in 22/23, 19/23, 8/19, 3/19, 1/19 and 3/23 cases, respectively. With the remaining antibodies no immunoreactivity was observed. MUC1 and low-molecular-weight CKs in conjunction with immunonegativity for high-molecular-weight CKs are the most diagnostically useful markers. MPD is caused by the epidermotropic spread of underlying tumour cells, whereas EMPD probably arises from intraepithelial cells of sweat gland origin. Targeted therapy with antibodies against EGFR (HER1), HER3 or HER4 is unlikely to prove of clinical value.
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