VEGF-B expression in human primary breast cancers is associated with lymphnode metastasis but not angiogenesis

Angiogenesis is essential for tumour growth and metastasis. It is regulated by numerous angiogenic factors, one of the most important being vascular e ndothelial growth factor (VEGF). Recently VEGF-B, a new VEGF family member that binds to the tyrosine kinase receptor flt-1, has been identified. Alth ough the importance of VEGF has been shown in many human tumour types, the contribution of VEGF-B to tumour neovascularization is unknown in any tumou r type, This study therefore measured the mRNA level of VEGF-B and its rece ptor flt-1 by ribonuclease protection assay and the pattern of VEGF-B expre ssion by immunohistochemistry in 13 normal breast samples and 68 invasive b reast 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 ass ociation between VEGF-B and node status (p = 0.02) and the number of involv ed 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), N o significant relationship was present between VEGF-B and flt-1 (p = 0.2) o r tumour vascularity (p = 0.4), VEGF-B was expressed mostly in the cytoplas m of tumour cells, although occasional stromal components including fibrobl asts and endothelial cells were also positive. No difference in VEGF-B expr ession was observed adjacent to regions of necrosis, in keeping with this V EGF family member not being hypoxically regulated. These findings suggest t hat VEGF-B may contribute to tumour progression by a non-angiogenic mechani sm, possibly by increasing plasminogen activators and hence metastasis, as has been described irt vitro. Measurement of VEGF-B together with other ang iogenic factors may identify a poor prognostic patient group, which may ben efit from anti-VEGF receptor therapy targeted to flt-1 (VEGFR1) as well as kdr (VEGFR2). Copyright (C) 2001 John Wiley & Sons, Ltd.