TY - JOUR
T1 - Multiple VEGF Family Members are Simultaneously Expressed in Ovarian Cancer
T2 - a Proposed Model for Bevacizumab Resistance
AU - van der Bilt, Arne R. M.
AU - van der Zee, Ate G. J.
AU - de Vries, Elisabeth G. E.
AU - de Jong, Steven
AU - Timmer-Bosscha, Hetty
AU - ten Hoor, Klaske A.
AU - den Dunnen, Wilfred F. A.
AU - Hollema, Harry
AU - Reyners, Anna K. L.
PY - 2012/8
Y1 - 2012/8
N2 - 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 omental metastases.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.
AB - 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 omental metastases.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.
KW - Ovarian cancer
KW - VEGF-A
KW - VEGF-B
KW - VEGF-C
KW - VEGF-D
KW - bevacizumab resistance
KW - ENDOTHELIAL-GROWTH-FACTOR
KW - GYNECOLOGIC-ONCOLOGY-GROUP
KW - PROGNOSTIC-SIGNIFICANCE
KW - FACTOR-C
KW - MICROVESSEL DENSITY
KW - TUMOR ANGIOGENESIS
KW - PHASE-II
KW - CARCINOMA
KW - STAGE
M3 - Article
SN - 1381-6128
VL - 18
SP - 3784
EP - 3792
JO - Current Pharmaceutical Design
JF - Current Pharmaceutical Design
IS - 25
ER -