Relationship between Co-expression of Vascular Endothelial Growth Factor and its Receptor, Kinase Insert Domain Containing Receptor and Tumor Angiogenesis in Invasive Carcinoma of the Cervix

OBJECTIVE The aim of the present study was to determine the expression of vascular endothelial growth factor (VEGF) and its receptor, kinase insert domain containing receptor (KDR), and their significance in regulating tumor angiogenesis in the early stages of cervical cancer.

METHODS Using the immunohistochemical SP method, the expression of VEGF and KDR was determined in the cancer cells. In addition, the microvessel density (MVD), labeled by CD34 in the tumor stroma, was examined in 18 cases of cervical intraepithelial neoplasms (CIN), 75 cases of early invasive cervix carcinomas (ICC) and 15 specimens of normal cervical epithelium (NCE).

RESULTS In ICC cases, VEGF and KDR were mainly expressed in the cellular membrane and/or cytoplasm of tumor cells, while expression of CD34 was found mainly in the vascular epithelial cells of the tumor stroma. The positive expression rate of VEGF and KDR, and the MVD increased remarkably from NCE through CIN to ICC (P<0.01). For the ICC group, in the patients with positive expression of VEGF and KDR, the MVD was significantly higher than those with negative expression of VEGF and KDR (P <0.05). Expression of VEGF in ICC was positively related to KDR expression (r=0.56, P<0.01). The MVD was also positively related to both the expression of VEGF (r=0.60, P<0.01), and KDR (r=0.33, P<0.01). In the cases with both positive expression of VEGF and KDR, the MVD was significantly higher than those in which there was negative expression of both (P<0.01).

CONCLUSION Expression of VEGF and its receptor KDR plays a key role in up-regulating tumor angiogenesis in cervical carcinoma. Co-overexpression of VEGF and KDR results in rapid tumor vasculogenesis. Detection of co-expression of VEGF and KDR may be of value in further understanding tumor angiogenesis and in searching for new targets for anti-angiogenesis therapy in invasive carcinoma of the cervix.