Upregulation of basic fibroblast growth factor in breast carcinoma and itsrelationship to vascular density, oestrogen receptor, epidermal growth factor receptor and survival

Background: Angiogenesis, the process whereby endothelial cells divide and migrate to form new blood capillaries, has been assessed in tumours by meas uring microvessel density. High microvessel density is a significant advers e prognostic factor in breast cancer. The angiogenic factor, basic fibrobla st growth factor (bFGF), has been associated with tumourigenesis and metast asis in several human cancers. There are few quantitative studies of bFGF e xpression in normal tissues compared to cancer. Patients and methods: We have measured bFGF levels in 149 human primary bre ast carcinomas and assessed the findings in relation to microvessel density , oestrogen receptor (ER) and epidermal growth factor receptor (EGFR). Basic FGF levels were measured by ELISA. Western blotting and immunohistoch emistry were carreid out to confirm the presence of bFGF. Results: Levels of bFGF were more than 10-fold higher in tumour cytosols co mpared to reduction mammoplasty tissue and 3-fold compared to non neoplasti c cytosols from the same breast as the tumour (P < 0.0001). Immunohistochem istry showed bFGF protein was localised exclusively in the stroma whereas n o bFGF staining was observed in the epithelial cells. High bFGF levels were significantly related to high ER (P = 0.01). Similarly, high bFGF levels w ere significantly related to low grade (P = 0.046) and to small tumour size (P = 0.04). No significant relationship was observed between bFGF and micr ovessel count, EGFR or age. In univariate analysis and in a Cox proportiona l hazard model bFGF did not reach significance for overall or relapse free survival. Conclusions: Our results show that although bFGF is elevated in breast carc inomas compared to normal breast tissue it is not related to microvessel de nsity and it is not an independent predictor of survival in breast cancer p atients. Basic FGF may be one of multiple factors that synergise with other growth factors such as VEGF to enhance angiogenesis.