Search

Our understanding of the pathogenesis of Paget's disease of the vulva and the breast remains limited. Current evidence supports the fact that angiogenesis plays an important role in the pathogenesis of several diseases. Therefore, we sought to define its role, as correlated with microvessel density, in Paget's disease of the vulva and the breast. Microvessels were analysed using anti-von Willebrand factor antibody in 105 cases of Paget's disease of the vulva and the breast comprising 71 cases of Paget's disease of the vulva, including 8 cases with invasive disease, and 34 cases of Paget's disease of the breast. The latter included 12 cases with DCIS, 5 cases with both DCIS and invasive carcinoma, and 6 with carcinoma alone. Eleven cases had no underlying tumour identified. Increased microvessel density was demonstrated in Paget's disease of the breast with DCIS and with carcinoma alone compared to Paget's disease of the breast alone, P < 0.08 and P < 0.013, respectively. There were no significant differences in microvessel density in the vulval cases. Neovascularisation is an important process in the development of Paget's disease of the breast. Other biological and molecular processes are more involved in the pathogenesis of Paget's disease of the vulva.

Aims: Loss of retinoblastoma protein expression and overexpression of cyclin D1 have been implicated in the development and progression of some cancers. Paget's disease of the vulva (PDV) and Paget's disease of the breast (PDB) are uncommon conditions and the pathogenesis of these diseases is still unclear. The aim was to examine the expression of the retinoblastoma and cyclin D1 proteins in PDV and PDB and to correlate any differences between PDV and PDB, and in the presence or absence of an underlying carcinoma., Methods and Results: Seventy-two archival cases of PDV including 10 with invasive disease and 36 cases of PDB were evaluated immunohistochemically for the expression of cyclin D1 and retinoblastoma protein. Forty-four percent (32/72) of cases of PDV showed loss of expression of the retinoblastoma protein, compared with 67% (24/36) of PDB cases. Fifty-nine percent (41/69) of PDV overexpressed cyclin D1. In PDB, 8% (3/34) overexpressed cyclin D1. There were no significant differences in the expression of retinoblastoma and cyclin D1 in PDV cases with or without underlying invasive disease. There were significant differences between the expression of retinoblastoma (P = 0.03) and cyclin D1 (P < 0.001) in PDV compared with PDB., Conclusions: The differences in the expression of cyclin D1 and retinoblastoma may indicate the differences in the pathogenesis of PDV and PDB.

Introduction: Most cases of anal carcinoma seem to develop from high grade anal intraepithelial neoplasia (AIN) caused by persistent anal warts. Similar pre-invasive epithelial genital lesions (e.g. those of the cervix and vulva) have been shown to be associated with increased angiogenesis. In this study we examined biopsies of anal lesions ranging from warts to invasive anal carcinoma, with the aim of assessing the degree of angiogenesis in pre-invasive anal lesions., Method: Samples from 70 patients (51 male) who had undergone excision biopsy or resection of anal wart lesions (20), low grade AIN (12), high grade AIN (27) and anal squamous cell carcinoma (SCC) (11) were studied. Samples (6) from normal HIV-anal skin were used as controls. The samples were stained for von Willebrand factor, a specific marker of endothelial cells. Angiogenesis was measured by microvessel density (MVD) analysis, quantifying the microvessels in the stroma adjacent to the epithelial lesion., Results: There was a statistically significant (P < 0.001) progressive increase in MVD between low grade AIN, high grade AIN and anal SCC. The difference in MVD between normal skin, warts and low grade AIN was not statistically significant., Conclusion: There are progressive abnormal patterns of angiogenesis in highly dysplastic lesions, similar to those found in cervical and vulvar pathology. These findings may have biological, prognostic and therapeutic implications.

Background: Paget's disease of the vulva and the breast are uncommon conditions. The pathogenesis underlying these diseases is still unclear. Vascular endothelial growth factor-A (VEGF-A), a potent angiogenic factor, has been demonstrated in a variety of tumour cell types and is thought to be involved in tumour expansion. Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) has also been shown to stimulate angiogenesis., Materials and Methods: Fifty-four cases of Paget's disease of the vulva, including 10 with an associated invasive adenocarcinoma, and 38 cases of Paget's disease of the breast, including 26 with available associated ductal carcinoma in situ (DCIS) and/or invasive carcinoma of the breast, were evaluated immunohistochemically for the expression of VEGF-A and PD-ECGF/TP., Results: VEGF-A was not expressed in Paget's disease of the vulva or breast. PD-ECGF/TP was expressed in 22 out of 54 (41%) cases of Paget's disease of the vulva. Four of the cases associated with invasive disease (40%) expressed PD-ECGF/TP. Twenty-one out of 38 (55%) cases of Paget's disease of the breast were positive for PD-ECGF/TP., Conclusion: Our data suggest that PD-ECGF/TP may have a role to play in the pathogenesis of Paget's disease of the vulva and the breast. The role of VEGF-A in Paget's disease of the vulva and the breast remains to be fully elucidated.