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.