Assessment of proliferating activity in Paget's disease of the nipple by double stain immunohistochemistry

Paget disease of the nipple is a rare disease characterized by the presence of malignant glandular cells within the squamous epithelium of the nipple. The most common hypothesis to explain the development of Paget's disease is an intraepithelial epidermotropic migration of malignant epithelial cells originating from an underlying intraductal carcinoma. Although the immunohistochemical properties of Paget cells in the nipple have been extensively studied, their proliferating characteristics remain paradoxically poorly studied. In the present study we have investigated the proliferating activity of Paget cells in the nipple by using double stain immunohistochemistry with both Ki-67 (a protein which is expressed in all active parts of the cell cycle) and cytokeratin 7 (a highly sensitive marker of Paget cells). Ten cases of Paget's disease and the associated intraductal carcinomas (n = 10) and/or invasive carcinomas (n = 4) were tested. The mean Ki-67 index was in Paget's disease (26% +/- 10). in intraductal carcinomas (23% +/- 8) and/or in invasive carcinomas (20% +/- 8) (p > 0.05). This is the first report to convincingly demonstrate by specific double stain immunohistochemistry that Paget's disease and underlying intraductal carcinomas share a close proliferating activity.