Tumor Angiogenesis in Uterine Cervical Neoplasia and Relation of Angiogenesis to Neoadjuvant Chemotherapy

Lee, I C; Won, J Y; Kim, S S; Kim, D H; Lee, T H; Jeon, S S; Kwak, J S; Cho, Y L

Abstract

Various clinical and histopathologic characteristics are currently used to obtain prognostic information about cervical carcinoma, but they do not predict accurately the outcome for individual patients. Thus, there is need to identify additional tumor characteristics that are able to predict more accurately the outcome for an individual patient with cervical cancer. Tumor microvessel density has recently been demonstrated to correlate strongly with disease aggressiveness in several types of malignancies. However, little is known of the significance of neovascularization in cervical cancer. In this study, we explored the relationship between microvessel count and progression of the cervical neoplasia, the correlation between response to neoadjuvant chemotherapy and tumor angiogenesis, and we investigated if tumor angiogenesis could serve as a prognostic factor in cervical carcinoma. Tumor tissues were obtained from 28 patients with cervical intraepithelial neoplasia and 46 patients with squamous cell carcinoma of the cervix. Microvessel were identified by immunohistochemical methods using monoclonal antibody QBEnd/10 to the CD34. In each case, three microscopic fields (x200) with the highest number of microvessels were counted and averaged. The results were as follows. Comparison of microvessel counts underlyng low grade lesion with microvessel counts of high grade lesion showed a statistically significant increase in the more advanced lesions (p<0.05). Patients whose tumor response to neoadjuvant chemotherapy were good had significantly higher microvessel counts than those showing poor response (145.53 47.72 vs 101.40 30.70, p<0.01). There was no correlation between microvessel count and tumor size, node status, lymphvascular invasion, depth of invasion, or parametrial invasion. In univariate analysis by log-rank test, vascular count was not significantly associated with disease free survival. Microvessel counts from postchemotherapy specimen showed lower tumor vascularity than prechemotherapy specimen but there was no significance. These results suggest that angiogenesis is an early, critical step in cervical neoplasm. Microvessel countingmay be a prognostic factor linked to tumor chemoresistance and may not be suitable for clinical use as a prognostic factor in cervical carcinoma.