Extramammary Paget disease of the vulva: immunohistochemical analysis of neoangiogenesis and epithelial-mesenchymal transition markers expression

Background: Extra-mammary Paget's disease of the vulva (EMPDV) is an infrequent chronic disease that often recurs. The aim of the study was to assess the presence of neoangiogenesis and the expression of epithelial-mesenchymal transition (EMT) markers in EMPDV, and their potential correlation with stromal invasion.Methods: All the women consecutively treated for EMPDV at our Institute, between January 2011 and December 2014, were studied for neoangiogenesis, analysed by microvessel density (MVD) using antibodies against CD31 and CD34. Immunohistochemical expression of E-/N-cadherin, beta-catenin and SLUG was also evaluated. In each slide, three fields with the highest number of capillaries and small venules were identified at low power. In these three fields, the highest vessel density (HVD) and the average vessel density (AVD) at 200x and 400x magnification were counted. Immunohistochemical reactions for non-vascular markers were semiquantitatively scored by two pathologists, using a three-tier scale.Results: Seventeen cases of EMPDV (including 10 cases of invasive disease) were included. The AVD at 200x and 400x and the HVD at 400x magnification were significantly associated with invasive EMPDV (p = 0.02, 0.03, 0.03 respectively). No significant correlation between MVD, EMT-markers expression and risk of recurrence was detected.Conclusion: These results indicate that MVD, as a measure of neoangiogenesis, may be associated with histological progression of EMPDV. EMT could also be linked to an invasive potential of EMPDV but larger series are required to confirm this hypothesis.