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pubmed-article:11241411pubmed:abstractTextAngiogenesis is essential for tumour growth and metastasis. It is regulated by numerous angiogenic factors, one of the most important being vascular endothelial growth factor (VEGF). Recently VEGF-B, a new VEGF family member that binds to the tyrosine kinase receptor flt-1, has been identified. Although the importance of VEGF has been shown in many human tumour types, the contribution of VEGF-B to tumour neovascularization is unknown in any tumour type. This study therefore measured the mRNA level of VEGF-B and its receptor flt-1 by ribonuclease protection assay and the pattern of VEGF-B expression by immunohistochemistry in 13 normal breast samples and 68 invasive breast cancers. Flt-1 expression was significantly higher in tumours than in normal breast (p=0.02) but no significant difference was seen in VEGF-B between normal and neoplastic breast (p=0.3). There was a significant association between VEGF-B and node status (p=0.02) and the number of involved nodes (p=0.01), but not with age (p=0.7), size (p=0.6), oestrogen receptor (ER) (p=0.2), grade (p=0.5) or vascular invasion (p=0.16). No significant relationship was present between VEGF-B and flt-1 (p=0.2) or tumour vascularity (p=0.4). VEGF-B was expressed mostly in the cytoplasm of tumour cells, although occasional stromal components including fibroblasts and endothelial cells were also positive. No difference in VEGF-B expression was observed adjacent to regions of necrosis, in keeping with this VEGF family member not being hypoxically regulated. These findings suggest that VEGF-B may contribute to tumour progression by a non-angiogenic mechanism, possibly by increasing plasminogen activators and hence metastasis, as has been described in vitro. Measurement of VEGF-B together with other angiogenic factors may identify a poor prognostic patient group, which may benefit from anti-VEGF receptor therapy targeted to flt-1 (VEGFR1) as well as kdr (VEGFR2).lld:pubmed
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pubmed-article:11241411pubmed:issn0022-3417lld:pubmed
pubmed-article:11241411pubmed:authorpubmed-author:HarrisA LALlld:pubmed
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pubmed-article:11241411pubmed:volume193lld:pubmed
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pubmed-article:11241411pubmed:pagination325-32lld:pubmed
pubmed-article:11241411pubmed:dateRevised2006-11-15lld:pubmed
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pubmed-article:11241411pubmed:year2001lld:pubmed
pubmed-article:11241411pubmed:articleTitleVEGF-B expression in human primary breast cancers is associated with lymph node metastasis but not angiogenesis.lld:pubmed
pubmed-article:11241411pubmed:affiliationAnatomical Pathology, Canterbury Health, Christchurch Hospital, Christchurch, New Zealand.lld:pubmed
pubmed-article:11241411pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:11241411pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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