Correlation of Vascular Endothelial Growth Factor Expression and Microvessel Density in Cervical Intraepithelial Neoplasia

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Abstract
Background: Angiogenesis (the formation of new blood vessels) appears to be required for the growth of invasive tumors, but little information exists about its role in the development of preinvasive lesions. We examined microvessel density and expression of vascular endothelial growth factor in specimens of cervical intraepithelial neoplasia (CIN), a preinvasive lesion of the uterine cervix, to determine whether a connection could be established between these parameters of angiogenesis and the grade of dysplasia (i.e., tissue abnormality). Methods: Sections of biopsy specimens from 83 patients with grades I–III CIN were examined retrospectively. Microvessels were localized by use of a polyclonal antibody directed against factor VIII-related antigen; vascular endothelial growth factor was detected by means of a monoclonal antibody. Reported P values are two-sided. Results: Highest microvessel densities and highest expression of vascular endothelial growth factor were found in a narrow border region between CIN lesions and the underlying stroma. A significant correlation was observed between high vascular endothelial growth factor expression and high microvessel density (Kendall's τ = 0.27; 95% confidence interval [CI] = 0.03–0.50; P = .018). Mean microvessel density values ± standard deviations for CIN I, CIN II, and CIN III lesions were 19.4 ± 5.8, 21.9 ± 7.0, and 34.1 ± 14.8, respectively (Kendall's τ = 0.46; 95% CI = 0.30–0.61; P<.0001). Corresponding values for vascular endothelial growth factor expression were 8.3 ± 3.5, 8.4 ± 2.0, and 12.2 ± 3.6, respectively (Kendall's τ = 0.41; 95% CI = 0.20–0.60; P<.0001). Conclusions: Our results are consistent with the idea that progression of cervical dysplasia is dependent on angiogenesis.