| Background: Paget's disease (PD) is an intra-epidermal adenocarcinoma seen over the nipple/areola (mammary Paget's disease MPD) or in extramammary body zones (extramammary Paget's disease EMPD). PD predominantly affects elder patients between 50 and 80 years old. MPD is an uncommon presentation of breast malignancy, accounting for 1%~3% of all the breast tumors. EMPD accounting for about 1% of vulvar malignancies and 6.5% of all cases of Paget's disease. Mammary and extramammary Paget's disease have similar clinical features and may mimic in?ammatory and infectious skin disorders. MPD and EMPD have similar pathological features that are characterized by the invasion of epidermis by Paget cells (PC). MPD is almost exclusively associated with ductal carcinoma in situ (DCIS), or invasive ductal carcinoma (IDC), whereas EMPD may be associated with an underlying (skin or visceral) malignancies occurs much less frequently. The cells of origin in MPD and EMPD have been the subject of controversy. Even though the standard treatment for EMPD is also surgical, the prognosis is not satisfactory, and there is a high recurrence rate. Recurrent disease after surgery might be a challenge.Objective: The aim of this study was, by the use of immunohistochemistry, to derive further information about the cell (s) of origin, and investigate candidates for possible targeted therapy to reduce recurrence rate. To evaluate the clinical and pathological features of PD and determine prognostic factors for survival and recurrence.Material and Methods: An retrospective review identified 42 patients with MPD and 20 patients with EMPD between January 1990 and December 2004 for clinical, pathologic, and treatment variables. Histopathologic samples from 42 patients with MPD and 20 patients with EMPD stained with antibodies against ER and PR, AR, E-cad, MUC5AC, and GCDFP-15 with immunohistoehemistry technique. We Use HercepTest to analyze expression of HER-2/neu. HER2/neu was graded on a scale from 0 to 3. A score of 3 was considered positive. For AR, ER, PR, E-cad, MUC5AC, and GCDFP15, a semi-quantitative scoring system was used. A score>10% was considered positive. Fisher's exact test was used to analyze the data. P-value of<0.05 was considered statistically significant.Results: Presence of a palpable mass, suspicious mammogram, axillary lymphnode metastases, and invasive cancer on histology were associated with survival of MPD. Invasion level and ill-defined margins were associated with recurrence of EMPD.In all PD cases CK7 and MUC1 were positive. In MPD cases ER, PR, AR, GCDFP-15, MUC5AC, HER-2, E-cad were positive in 11.9% (5/42), 0% (0/42), 35.7% (15/42), 50% (21/42), 16.7% (7/42), 88.1% (37/42), 64.3% (27/42) cases, respectively. In EMPD cases ER, PR, AR, GCDFP-15, MUC5AC, HER-2, E-cad were positive in 0% (0/8), 0% (0/20), 80% (16/20), 80% (16/20), 60% (12/20), 50% (10/20), 45% (9/20) cases, respectively.Conclusions: 1. Paget's disease (PD) is an primary intra-epidermal adenocarcinoma in nature. 2. These data suggest that MPD and EMPD are biologically different. 3. The knowledge about frequent expression of AR and HER-2/neu in Paget's disease could lead to the development of a new adjuvant therapy, particularly in patients with recurrent disease. 4. Presence of a palpable mass, suspicious mammogram, axillary lymphnode metastases, and invasive cancer on histology were associated with a significantly worse outcome. Invasion level and ill-defined margins is are important prognostic factors in EMPD.
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