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 Gl/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.

Plasma concentration of angiopoietin-1, angiopoietin-2 and Tie-2 in cervical cancer.

PURPOSE OF INVESTIGATION: Angiogenesis is important in the promotion and progression of malignancy. The formation of new blood vessels is coordinated by many factors, angiopoietins among others. Overexpression of angiopoietins has been observed in various tumors. The aim of the study was to evaluate plasma concentration of Ang-1, Ang-2 and Tie-2 in cervical cancer. METHODS: The study group consisted of 34 patients with cervical cancer and the control group of 20 healthy volunteers. Plasma concentrations of Ang-1, Ang-2 and Tie-2 were evaluated by ELISA. RESULTS: Plasma concentrations of Ang-1, Ang-2, Tie-2 and Ang-1/Ang-2 ratios were significantly higher in cervical cancer patients than in controls. Although there was no correlation between concentration of Ang-1, Ang-2, Tie-2 and clinical stage (FIGO), the Ang-1/Ang-2 ratio was higher in Stage I than in II-III. Ang-1 correlated positively with Ang-2 and Tie-2 in a subgroup with Stage II-III and Ang-2 with Tie-2 in a subgroup with Stage I. CONCLUSION: Plasma concentrations of Ang- 1, Ang-2 and Tie-2 may be useful additional tumor markers in cervical cancer.

Influence of surgical resection on plasma endoglin (CD105) level in non­small cell lung cancer patients.

BACKGROUND AND AIM: Endoglin is a proliferation-associated antigen on endothelial cells and essential for angiogenesis. Soluble endoglin (s­endoglin), formed by proteolytic cleavage of ectodomain of membrane receptor could be an indicator of tumor­activated endothelium. The aim of present study was to analyze changes of s­endoglin level in plasma of lung cancer patients following surgical resection and to estimate the correlation of s­endoglin with other soluble receptors, sTie2 and sVEGF R1. PATIENTS AND METHODS: The study group consisted of 37 patients with stage I of non-small cell lung cancer. Plasma concentrations of s­endoglin, sTie2 and sVEGF R1 were evaluated by ELISA, three times: before surgical resection and on postoperative day 7 and 30. RESULTS: The median of s­endoglin concentration decreased significantly on postoperative day 7 when compared with preoperative level and next increased on 30(th) day and it was comparable with that before surgery. s-Endoglin correlated with another soluble receptors, with sTie2 both before surgery (r=0.44) and on postoperative day 7 (r=0.52) and on 30(th) day (r=0.58), with sVEGF R1 - only on postoperative day 7 (r=0.75). CONCLUSION: The increased level of serum endoglin in lung cancer patients compared to controls and its changes after surgical treatment suggest potential application of soluble form of endoglin as potential tumor marker.