Objective: Insight into the expression of multiple vascular endothelial growth factor (VEGF) family members can support the
implementation of anti-angiogenic therapy. This study aimed to assess VEGF family member expression in ovarian cancers and related
Methods: Tissue microarrays encompassing 270 primary cancers and 112 paired metastases were immunostained for VEGF-A, VEGF-B,
VEGF-C and VEGF-D. Staining intensities were categorized as absent, weak, moderate or strong. Expression was related to clinicopathological
characteristics and survival.
Results: Immunohistochemical positivity (defined as moderate or strong expression) was observed for VEGF-A in 90%, VEGF-B in 4%,
VEGF-C in 41% and VEGF-D in 55% of the primary ovarian cancers. VEGF-A expression correlated with VEGF-C and VEGF-D expression
(P < 0.01). Simultaneous positivity for VEGF-A and VEGF-C or VEGF-D was observed in 38% and 54% of the cancers, respectively.
Metastases showed positivity for VEGF-A in 78%, VEGF-B in 5%, VEGF-C in 26% and VEGF-D in 45% of cases. VEGF
family member expression showed no independent prognostic significance in multivariate survival analysis.
Conclusion: VEGF-A, VEGF-C and VEGF-D are widely and often simultaneously expressed in ovarian cancer, which may contribute to
bevacizumab resistance. Measuring their expression could support a rational, individualized choice of anti-angiogenic therapy and might
be of predictive value. Studies are warranted to determine whether combinatorial analysis of VEGF family member expression can be
used to predict anti-angiogenic drug efficacy.