Extramammary Paget disease of the vulva: immunohistochemical analysis of neoangiogenesis and epithelial-mesenchymal tran
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RESEARCH
Open Access
Extramammary Paget disease of the vulva: immunohistochemical analysis of neoangiogenesis and epithelialmesenchymal transition markers expression Lara Alessandrini1†, Nicolò Clemente2†, Tiziana Perin1, Giorgio Giorda2, Vincenzo Canzonieri1,3*† and Francesco Sopracordevole2†
Abstract 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 epithelialmesenchymal 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, β-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 200× and 400× 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 200× and 400× and the HVD at 400× 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. Keywords: Paget disease, Vulva, Neoangiogenesis, EMT, Microvessel density, HVD, AVD
Background Extra-mammary Paget’s disease of the vulva (EMPDV) is an infrequent chronic disease that often recurs and accounts for less than 1% of vulvar neoplasms [1]. It is characterized by peculiar cells (so-called “Paget cells”) with pale large cytoplasm and prominent nucleoli, that are located in single cells or in clusters throughout the epithelium, and may form gland-like structures [2]. In * Correspondence: [email protected] † Equal contributors 1 Pathology Unit - CRO - IRCCS, National Cancer Institute, Aviano, Italy 3 Pathology Unit - CRO - IRCCS, National Cancer Institute, Via Franco Gallini, 2, I-33081 Aviano, (PN), Italy Full list of author information is available at the end of the article
the pathologic report of EMPDV, it is mandatory to evaluate the presence/absence of stromal invasion, which is defined by the occurrence of dyscohesive neoplastic cells infiltrating the underlying dermis or submucosa and to distinguish between superficially invasive carcinoma (stromal invasion ≤1 mm, according to the International Federation of Gynecology
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