Angiogenesis in anal warts, anal intraepithelial neoplasia and anal squamous cell carcinoma.

Abstract

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. 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. 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. 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.