Prognostic Significance of Angiogenic Factors in Uterine Cervical Cancer

Background/Aim: Angiogenesis is pivotal in tumour development and progress, and targeted tumour therapies, such as bevacizumab, have shown promising results. However, in unselected patient populations, the treatment with angiogenesis-targeted combination regimens is marred by a variable response, non-negligible toxicity and questionable economy. The present study summarizes research to identify individual circulating angiogenic factors as markers for disease severity and possibly treatment response. Patients and Methods: A total of 125 patients with cervical cancer from the ongoing cervical cancer monitoring database of the University Hospital Charite, Berlin, Germany, were included. Information obtained from the database included tumour stage, malignancy grade, presence of nodal metastases, lymph vessel invasion, patient age, HER2, HPV, smoking and menopausal status, and serum concentrations of vascular endothelial growth factor (VEGF), VEGF-D, VEGF-C, endoglin, endostatin, angiogenin, basic fibroblast growth factor (FGFb), vascular endothelial growth factor receptor (VEGF-R1), VEGF-R2, soluble inter-cellular adhesion molecule 1 (sICAM 1), soluble vascular adhesion molecule 1 (sVCAM 1), insulin-like growth factor 1 (IFG-1) and insulin like growth factor binding protein 3 (IGF-BP3). Results: There was a clear association of angiogenic factor concentrations with stage of disease. Angiogenin showed an independent discrimination for cervical intraepithelial neoplasia (CIN) and invasive stages, and endoglin did so for invasive stages vs. recurrent disease. However, none of the potential markers under investigation was anywhere near selective enough to allow for a clinically meaningful prediction of prognosis or response. Conclusion: The association of circulating angiogenic factors with disease progression in cervical cancer is confirmed, but its utility for prognosis prediction and patient stratification for targeted therapies is doubtful.