Expression of PTEN in the progression of cervical neoplasia and its relation to tumor behavior and angiogenesis in invasive squamous cell carcinoma

BACKGROUND AND OBJECTIVES: Loss of PTEN expression has been associated with tumor progression and adverse patient outcome. The purpose of this study was to evaluate PTEN expression in the successive steps of progression in cervical neoplasia and to determine its correlation with tumor angiogenesis and clinicopathologic features in squamous cell carcinoma of the uterine cervix. METHODS: Immunohistochemical staining with anti-PTEN antibody was performed in a total of 160 patients with 12 normal cervical epithelium, 63 cervical intraepithelial neoplasia (33 CIN I, 30 CIN III), and 85 cervical squamous cell carcinomas. Microvessels were immunohistochemically labeled with an antibody for CD34. Computerized image analysis was used to evaluate microvessel density (MVD). RESULTS: Reduced PTEN expression progressively increased along the continuum from normal epithelium to squamous cell carcinoma (P < 0.01). There was no significant correlation between PTEN expression and MVD. On univariate analysis, stage and reduced PTEN expression were significant prognostic factors for both disease-free and overall survival. However, stage was the only independent prognostic factor by multivariate analysis. CONCLUSIONS: Our results suggest that tumor progression in the cervical epithelium is accompanied by loss of PTEN protein expression. Reduced PTEN expression is not associated with tumor angiogenesis of squamous cell carcinoma of the uterine cervix.