In vitro vascular tube formation testing as a tool for treatment individualisation in patients with cervical cancer.

BACKGROUND/AIM: Targeted tumour therapies are promising, but their results in unselected patient populations are modest and tumour growth and metastasis may be promoted rather than suppressed in some cases. The present study investigates the suitability of vascular in vitro tube formation as a tool for the identification of cervical neoplasms that will respond to bevacizumab therapy. PATIENTS AND METHODS: Fifteen patients with recurrent cervical cancer selected from the ongoing cervical cancer monitoring database of the Charité University Hospital Berlin, Germany, were included. Information obtained from the database included tumour stage, malignancy grade, presence of nodal metastases, lymph vessel invasion, patient age and menopausal status and serum concentrations of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), endostatin and vascular endothelial growth factor receptor 1 (VEGF-R1). Vascular tube formation was assessed with cultured human umbilical vein epithelial cells. RESULTS: Five patients showed a positive, 5 an inverse and 5 no in vitro response to bevacizumab. Tube length showed a marked and significant dependency on bevacizumab response. Besides tube length, VEGF-R1 concentration was the only variable with some correlation to bevacizumab response, with high levels especially for inverse responders. CONCLUSION: The identification of patients with a likely benefit from targeted therapies is crucial. Tube formation shows substantial potential, but its utility needs to be confirmed in studies on the clinical rather than in vitro response to bevacizumab.

The utility of an in vitro angiogenesis score for prognosis assessment in patients with cervical cancer.

BACKGROUND/AIM: Angiogenesis plays a key role in tumour growth and metastasis. Expression of angiogenic factors has been suggested as a marker for tumour malignity, and may help to assess a patient's individual prognosis. The present study examines the relationship between angiogenic factor expression, an angiogenesis-based histoscore and clinical tumour criteria. PATIENTS AND METHODS: A total of 81 patients with cervical cancer who underwent follow-up examinations between October 2002, and June 2005, were enrolled, and serum samples were examined for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), endostatin and VEGF-Receptor1 by means of an ELISA. Based on an endothelial-cell proliferation assay, an angiogenesis score was calculated. RESULTS: Higher endostatin and VEGF expressions indicated advanced disease, and VEGF allowed for a reliable distinction between patients with non-invasive and these with recurrent disease. There were some plausible correlations between the angiogenesis score and clinical criteria and individual angiogenic factors, but the score's discriminating power appears to be limited. CONCLUSION: The utility of angiogenesis factor testing notwithstanding, the value of an angiogenesis score for the identification of patients with a worse prognosis, and thus a resulting benefit from more aggressive treatment, is arguable.