Abstract 3005: Vascular endothelial growth factor A - a systematic review and meta-analysis of expression patterns in breast cancer
Authors: Adams Arthur , Vermeulen Jeroen , Zuithoff Peter , Wall Elsken Van der , Lamberts Laetitia , Vries Elisabeth de , Jong Johannes de , Dam Gooitzen Van , Diest Paul J. van , Mali Willem P.Th.M. , Elias Sjoerd G. 
Published: May 2015

Abstract
Background
Vascular Endothelial Growth Factor-A (VEGF-A), pivotal for neo-angiogenesis, is an interesting target for breast cancer molecular imaging. To assess its potential clinical value, we performed a systematic review and meta-analysis of VEGF-A expression rates in normal breast tissue, benign and (pre-)invasive breast disease, and investigated associations with clinicopathological characteristics.
Methods
We systematically searched EMBASE and MEDLINE for articles describing VEGF-A expression in breast disease assessed by immunohistochemistry (IHC) or Enzyme-Linked Immunosorbent Assay (ELISA). We pooled IHC expression rates with random-effects models and applied meta-regression to identify associations with clinicopathological characteristics. We summarized findings for ELISA results.
Results
Of 2,711 unique articles retrieved, 157 studies described IHC results (16,046 tissue samples). Pooled expression rates were lower in studies applying antibody clone VG1 (-21%, p=0.018) or C-1 (-24%, p=0.016), compared to A-20. Expression compared to invasive carcinoma was lower in normal tissue (-51%, p&lt;0.001) and benign breast diseases (-34%, p&lt;0.001), but comparable for carcinoma in situ (+5%, p=0.289). Expression rates increased with tumour grade (II: +14%, p&lt;0.001; III: +25%, p&lt;0.001), stage (II: +11%, p&lt;0.001; III: +22%, p&lt;0.001), size (T3/4: +11%, p=0.004), HER2-positivity (+14%, p&lt;0.001), lymph node positivity(+11%, p&lt;0.001), and decreased in hormone receptor positive (PR-positive: -7%, p&lt;0.001; ER-positive:-8%, p&lt;0.001) and lobular cancers (-14%, p&lt;0.001). Substantial heterogeneity was observed in study results. Furthermore, expression rates strongly depended on VEGF-A positivity threshold. VEGF-A levels assessed by ELISA (42 studies, 8,498 samples) were highly variable.
Conclusion
Although reported VEGF-A expression rates in breast cancer were variable, we found significant correlations with clinicopathological characteristics indicating aggressive disease. Also, expression rates were low in normal breast tissue and benign breast disease. As expression rates strongly depended on VEGF-A positivity - arguing against an on/off phenomenon - applicability of VEGF-A for molecular imaging purposes will depend on sensitivity of the molecular imaging modality, target population, and envisioned applications.
Acknowledgment
This research was supported by the Center for Translational Molecular Medicine (MAMMOTH).
Citation Format: Arthur Adams, Jeroen Vermeulen, Peter Zuithoff, Elsken Van der Wall, Laetitia Lamberts, Elisabeth de Vries, Johannes de Jong, Gooitzen Van Dam, Paul J. van Diest, Willem P.Th.M. Mali, Sjoerd G. Elias. Vascular endothelial growth factor A - a systematic review and meta-analysis of expression patterns in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3005. doi:10.1158/1538-7445.AM2014-3005