title: The role of HER-2/neu oncogene and vimentin filaments in the production of the Paget's phenotype.
abstract: The histogenesis as well as the biological and molecular differences in mammary Paget's disease (MPD) and extramammary Paget's disease (EPD) are not well understood. HER-2/neu oncogene overexpression is associated with poor prognosis in breast cancer patients. It is also believed that the spread of Paget's cells through the epidermis is induced by a motility factor that acts via the HER-2/neu receptor. However, previous studies on HER-2/neu expression in MPD and EPD have given conflicting results. Recent studies have suggested that vimentin expression in breast cancer confers a more aggressive phenotype with a possible role in tumor invasion and metastasis. We examined 58 cases of MPD and EPD for HER-2/neu overexpression and vimentin status to study the role of these markers in the production of the Paget's phenotype. Thirty-five of the 38 cases (92.1%) of MPD were associated with an underlying carcinoma, while none of the cases of EPD were associated with an underlying malignancy. Thirty-six of the 38 cases of MPD (94.7%) overexpressed the HER-2/neu oncoprotein and 17 cases (44.7%) showed vimentin expression. In contrast, only 1 of the 20 cases of EPD (5%) showed positivity for HER-2/neu oncoprotein and all were negative for vimentin. Our results indicate that the cell motility enhancing effect of HER-2/neu oncoprotein and possibly vimentin plays a significant role in the pathogenesis of MPD which appears to be a pagetoid spread of an underlying ductal malignancy (secondary), while EPD is an in situ malignant transformation of a totipotential epidermal cell or glandular epithelium.
authors: Department of Pathology, Sunnybrook and Women's College Health Sciences Center, Toronto, Ontario, Canada. wedad.hanna@sw.ca
authors: Wedad
authors: W
authors: Hanna
authors: Salem
authors: S
authors: Alowami
authors: Abha
authors: A
authors: Malik
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008499:Medical Records; D009518:New York; D009864:Ontario; D010145:Paget Disease, Extramammary / Q000235:genetics*; D010144:Paget's Disease, Mammary / Q000235:genetics*; D010641:Phenotype; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D014746:Vimentin / Q000235:genetics*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D014746:Vimentin