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Background: While macrophages (CD68+) have been associated with angiogenesis in some inflammatory and neoplastic processes by increasing the release of vascular endothelial growth factor (VEGF), their role in anal intraepithelial neoplasia (AIN) and anal squamous cell carcinoma has not been established. This study records macrophage infiltration in anal pre-invasive and invasive lesions in HIV+ and HIV- populations, and determines their relationship with angiogenesis., Materials and Methods: Sixty patients (31 HIV+) with AIN and anal SCC were studied. Paraffin sections were stained for CD68, VEGF and von Willebrand factor. The density of CD68 cells, the expression of VEGF and angiogenesis were quantified, and compared amongst groups and between HIV+ and HIV- populations., Results: All three parameters increased linearly as the lesions became more dysplastic, in HIV+ and HIV- groups. The CD68 count was statistically lower in HIV+ (p<0.005) compared with HIV- groups, while the differences in VEGF expression and in angiogenesis were not significant between HIV+ and HIV- populations., Conclusion: There was a significant decrease of macrophage infiltrate in the HIV+ group. The relative increase in VEGF expression and angiogenesis in the face of lower macrophage infiltration in HIV+ patients may be explained either by a greater release of angiogenic factors by macrophages, or by VEGF expression not being solely dependent on macrophage activation.

Background: Anal squamous cell carcinoma (SCC) develops from dysplastic anal warts. This study quantifies the expression of p53 and Ki67 in pre-invasive and invasive anal lesions., Materials and Methods: Samples of 70 patients with anal warts (n = 20), low grade anal intraepithelial neoplasia (LG AIN) (n = 12), high grade anal intraepithelial neoplasia (HG AIN) (n = 27) and anal SCC (n = 11) were stained using immunohistochemical techniques. Eight patients with normal anal skin were used as controls., Results: Both the expression of p53 and Ki67 increased significantly (p < 0.001) and gradually as the lesions became dysplastic and invasive. The main increase in p53 expression was as the lesions progressed from anal warts (7.38 +/- 11.93-mean +/- SD) to low grade AIN (20.778 +/- 13.14)., Conclusion: p53 is involved in the progression of anal cancer and its expression increases from early in the development of pre-invasive anal lesions. p53 and Ki67 may be useful markers of early dysplasia and should be considered in the screening of high risk patients.

Squamous cell carcinoma of the vulva (SCC) accounts for about 4% of all gynaecological malignancies. It has an incidence of about 1.8 per 100,000. However, after the age of 75 the incidence of vulvar carcinoma peaks at approximately 20 per 100,000, making it as common as cervical carcinoma. Benign and pre-malignant vulvar lesions can be broadly divided into non-neoplastic epithelial disorders of the vulva (NNEDV), vulvar intraepithelial neoplasia (VIN) and Paget's disease of the vulva (PDV). NNEDV lesions include lichen sclerosus (LS) and squamous hyperplasia (SH). To date no solid prognostic tools are available to predict which pre-malignant vulvar lesions will progress to SCC. About 4.5% of patients develop SCC following a history of LS and ca. 4% of treated VIN lesions go on to become vulvar SCC. In PDV, 28% of patients have an underlying cancer. Angiogenesis, the development of new blood vessels from existing vasculature, is an essential component of solid tumour growth and metastasis. Several angiogenic factors are expressed by many tumours, suggesting that tumours promote their own vascularisation by activating the host endothelium. This review follows the progress of research in angiogenesis in vulvar disease as assessed by a variety of methods, such as in situ hybridisation (ISH), microvessel density measurements (MVD), immunohistochemically-detected angiogenic growth factor expression, including vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP), and serum concentrations of VEGF. Thus, the potential of angiogenesis as a prognostic and predictive tool for identifying which pre-malignant lesions could progress to SCC is discussed. A relatively high MVD and strong VEGF expression may serve as prognostic indicators of survival in invasive SCC. MVD and VEGF expression are also predictive factors in identifying which VIN lesions are more likely to become invasive. However VEGF is not a predictive marker in cases of LS likely to progress to carcinoma. The expression of PD-ECGF/TP in all types of lesions tested prevents its use as a prognostic tool, unlike VEGF. However, PD-ECGF/TP is involved in PDV pathogenesis, but is not a marker of the malignant progression of PDV. In PDV, VEGF was not expressed even in those cases associated with invasive disease. Serum concentrations of VEGF play a functional role in vulvar carcinogenesis. Although associated with impaired disease-free and overall survival, pre-treatment serum concentrations of VEGF are not an independent predictor of outcome in patients with vulvar cancer. These studies suggest that further angiogenic research will be important in both the therapy and prognosis of malignant and pre-malignant vulvar disease.