Expression of the vascular endothelial growth factor (VEGF) gene in epithelial ovarian cancer: an approach to anti-VEGF therapy.

摘要

AIM: A monoclonal antibody that targeted vascular endothelial growth factor (VEGF) resulted in a dramatic suppression of tumor growth in vivo, which led to the development of bevacizumab, a humanized variant of anti-VEGF antibody, as an anticancer agent. The aims of this study were to clarify the significance of VEGF gene expression in relation to clinicopathological parameters and to identify potential candidates for anti-VEGF therapy with bevacizumab. PATIENTS AND METHODS: VEGF gene expression was analyzed by real-time quantitative reverse transcription-polymerase chain reaction in 178 surgical epithelial ovarian cancer specimens. This gene expression was correlated with clinicopathological parameters and patient survival. RESULTS: The median VEGF gene expression level and range relative to GAPDH were 0.147 and 0.016-2.44, respectively. Patients were dichotomized into two groups with low and high expression levels by using the median value as the cutoff. VEGF gene expression did not affect prognosis of patients overall (p = 0.541). Although statistical significance was not noted, we found the prognosis of patients with high VEGF gene expression tended to be worse than that of those with low VEGF gene expression by univariate Cox regression analysis (p = 0.085) in patients with stage III-IV cancer. Macroscopic residual disease (positive; p = 0.012) was significantly associated with poor prognosis in univariate Cox regression analysis in patients with stage III-IV cancer. Moreover, presence of macroscopic residual disease was positively associated with VEGF gene expression (p = 0.030) in patients with stage III-IV cancer. CONCLUSION: Patients with epithelial ovarian cancer with tumors with positive macroscopic residual disease and high VEGF gene expression could be potential candidates for anti-VEGF therapy with bevacizumab.