Labeling of microvessel density, lymphatic vessel density and potential role of proangiogenic and lymphangiogenic factors as a predictive/prognostic factors after radiotherapy in patients with cervical cancer

Introduction: Angiogenesis, formation of a new blood vessel from the existing vascular network, is essential for tumor growth, progression and metastasis. Vascular endothelial growth factor (VEGF) has been identified to be one of the most important factors of angiogenesis. VEGF-C, a novel member of the family, is a relatively specific lymphangiogenic growth factor. It is tempting to suggest that cervical cancer is one of the most common malignancies in a woman's life. Its prognostic factors are tumor stage, lymph node status, histologic type, level of hemoglobin. However, little is known about prognostic or/and predictive significance of angiogenesis in cervical cancer. Objective: This prospective study is an attempt to evaluate serum VEGF-A, VEGF-C, microvessel density (MVD), and lymphatic vessel density (LMVD) in cervical cancer and the correlations with clinicopathologic features. Material and Methods: Blood samples were collected from 58 patients affected by FIGO I-IV stage cervical cancer, who were admitted to the Department of Oncology and Brachytherapy Collegium Medicum in Bydgoszcz of Nicolaus Copernicus University. Serum VEGF-A/VEGF-C concentrate was determined by means of a quantitative sandwich enzyme immunoassay (ELISA). All tumor samples were taken from cross section during the first brachytherapy. Then they were examined by immunohistochemical studies with podoplanin antibody and anti-CD31 antibody. The present analysis was used to evaluate MVD and LMVD. Results: The median serum VEGF-A was 734.76 pg/ml (range from 86.39 pg/ml - 2200.00 pg/ml), and VEGF-A was only correlated with after treatment hemoglobin concentration (p = 0.046, R = -0.3450). The median serum VEGF-C was 145.72 pg/ml (range 131.08 -233.60 pg/ml). Serum VEGF-C levels measured in patients were associated with primary tumor size. We observed significantly higher serum VEGF-C in localized disease (FIGO I, II) in comparison to advanced tumors (232.44 pg/ml vs 152.45 pg/ml; p = 0.034). The median LMVD was 6.25 (range 3.5-10.0) and median blood vessel density was 12.5 (range 9.5-23.0). We found significantly higher lymphatic vessel density in patients with G1/G2 grade of differentiation than in those with G3 (9.93 vs 6.25; p = 0.0398). We observed a statistically significant correlation between MVD and LMVD; (p = 0.032). Conclusion: In conclusion, our study suggests that serum VEGF-A, VEGF-C, LMVD and MVD play an important role in tumor growth and progression in cervical cancer. Nonetheless, further studies are essential to explore the underlying mechanism.

Cervical cancer; Angiogenesis; VEGF; Microvessel density

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