Prognostic significance of epithelial-stromal vascular cuffing and microvessel density in squamous cell carcinoma of the uterine cervix

Objective. Tumor angiogenesis has been shown to play an important role in tumor growth and metastasis. This study examines the prognostic significance of two histological markers of angiogenesis, i.e., vascular cuffing (VC), a bead-like arrangement of microvessels closely surrounding microscopic tumor nests, and microvessel density (MVD), the number of microvessels in a unit area, in cervical squamous cell carcinoma. Methods. One hundred twenty-two specimens from surgically resected uteri with cervical squamous cell carcinoma were histologically reviewed and immunostained for CD34. VC was graded into 'none,' 'incomplete,' and 'complete.' The MVD was determined by counting the microvessels with a light microscope within a x200 field area where neovascularization occurred most actively. Stromal inflammation was also split into three grades. The relationship of VC or MVD to clinicopathological prognostic factors such as FIGO stage, cervical stromal invasion, lymph-vascular space invasion, pelvic lymph node metastasis, and parametrial invasion was evaluated using univariate and multivariate analyses. Results. The patients with a complete VC pattern showed a significantly worse prognosis compared to those with a pattern graded as either none or incomplete (P < 0.011 and P < 0.0001, respectively). The Cox regression analysis revealed the complete VC pattern, together with parametrial invasion, to be an independent prognostic indicator for overall survival. MVD and the grading of stromal inflammation showed no significant relationship with VC or overall survival. Conclusions. The complete VC pattern may therefore be a useful prognostic indicator in cervical squamous cell carcinoma.