Angiogenesis in pre-malignant conditions.

Angiogenesis is an essential process involved in the normal growth and differentiation. In its defective and excessive form, angiogenesis is a crucial event in the progression of many human diseases. Excessive angiogenesis was largely investigated in psoriasis, arthritis, diabetic retinopathy and malignant tumours. Soon after the discovery of angiogenic factors and their inhibitors, the angiogenesis jumped from the experimental studies to clinical application. Tumour-associated angiogenesis is nowadays considered as a priority in oncology based on numerous evidences that showed a significant reduction in tumour growth following anti-angiogenic therapy. However, few data are available on pre-malignant conditions. First evidences on angiogenesis in pre-malignant lesions came from the evaluation of microvessel density (MVD). MVD was found to be significantly increased in a relatively large spectrum of pre-malignant squamous cell lesions, such as in the oral mucosa, skin, uterine cervix, vulva and anal canal. For many of them, a correlation was found between MVD and the expression of vascular endothelial growth factor (VEGF). Based on these data, it was suggested that tumour angiogenesis is not necessarily a characteristic of invasive tumour, but may be an early event during tumourigenesis. Additional evidences came from pre-malignant lesions of glandular epithelia, in which the angiogenic switch was demonstrated by the immunohistochemical expression of VEGF in gastric metaplasia and dysplasia, in atypical adenoma of the colon, atypical hyperplasia and carcinoma in situ of the breast and others. Actually, there are convincing evidences for an active angiogenesis in many cases with pre-malignant conditions, and this supports a more accurate evaluation of different chemopreventive agents.