Angiogenesis is associated with vascular endothelial growth factor expression in cervical intraepithelial neoplasia

Squamous cell carcinoma of the cervix (SCC) is preceded by a premalignant condition known as cervical intraepithelial neoplasia (CIN). The majority of cases of CIN regress spontaneously; however, methods are needed to identify those lesions likely to progress. Increased blood vessel density, signifying angiogenesis, is an independent prognostic indicator in a number of cancers, although little is known about its significance in premalignant lesions. The aim of the present study was to determine the relationship between vessel density, expression of the potent angiogenic factor vascular endothelial growth factor (VEGF) and CIN grade. Using immunohistochemistry, mean vessel density (MVD) and VEGF expression were assessed in samples from 54 patients who had undergone cone biopsy for CIN or hysterectomy for SCC and from 16 patients with no cervical pathology. There were significant increases in MVD and VEGF expression from normal cervix through CIN I to CIN III to invasive SCC, but no difference in mean vessel diameter between groups. There was a strong correlation between mean vessel density and VEGF expression, and both were associated with histological grade of CIN. The original MVDs for a small group of patients later presenting with recurrent disease were found to be equal to or greater than the mean for their histological grade. We conclude that the onset of angiogenesis is an early event in premalignant changes of the cervix due, in part, to enhanced expression of VEGF by the abnormal epithelium.