多种 VEGF 家族成员在卵巢癌中同时表达：贝伐单抗耐药的一种假说。

Multiple VEGF family members are simultaneously expressed in ovarian cancer: a proposed model for bevacizumab resistance.

机构信息

Department of Medical Oncology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.

出版信息

Curr Pharm Des. 2012;18(25):3784-92. doi: 10.2174/138161212802002661.

DOI:10.2174/138161212802002661

PMID:22591424

Abstract

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.

摘要

目的

深入了解多种血管内皮生长因子（VEGF）家族成员的表达情况，有助于实施抗血管生成治疗。本研究旨在评估卵巢癌及其相关网膜转移灶中 VEGF 家族成员的表达情况。

方法

利用包含 270 例原发性癌症和 112 对配对转移灶的组织微阵列，对 VEGF-A、VEGF-B、VEGF-C 和 VEGF-D 进行免疫染色。将染色强度分为无、弱、中或强。分析表达与临床病理特征和生存的关系。

结果

90%的原发性卵巢癌中 VEGF-A 免疫染色阳性（定义为中或强表达），4%的卵巢癌中 VEGF-B 阳性，41%的卵巢癌中 VEGF-C 阳性，55%的卵巢癌中 VEGF-D 阳性。VEGF-A 的表达与 VEGF-C 和 VEGF-D 的表达相关（P<0.01）。同时 VEGF-A 和 VEGF-C 或 VEGF-D 阳性的肿瘤分别占 38%和 54%。转移灶中 VEGF-A 阳性率为 78%，VEGF-B 阳性率为 5%，VEGF-C 阳性率为 26%，VEGF-D 阳性率为 45%。在多变量生存分析中，VEGF 家族成员的表达无独立预后意义。