Upregulation of basic fibroblast growth factor in breast carcinoma and its relationship 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 measuring microvessel density. High microvessel density is a significant adverse prognostic factor in breast cancer. The angiogenic factor, basic fibroblast growth factor (bFGF), has been associated with tumourigenesis and metastasis in several human cancers. There are few quantitative studies of bFGF expression in normal tissues compared to cancer.


METHODS
We have measured bFGF levels in 149 human primary breast 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 immunohistochemistry were carried out to confirm the presence of bFGF.


RESULTS
Levels of bFGF were more than 10-fold higher in tumour cytosols compared to reduction mammoplasty tissue and 3-fold compared to non neoplastic cytosols from the same breast as the tumour (P < 0.0001). Immunohistochemistry showed bFGF protein was localised exclusively in the stroma whereas no bFGF staining was observed in the epithelial cells. High bFGF levels were significantly related to high ER (P = 0.01). Similarly, high bFGF levels were significantly related to low grade (P = 0.046) and to small tumour size (P = 0.04). No significant relationship was observed between bFGF and microvessel count, EGFR or age. In univariate analysis and in a Cox proportional hazard model bFGF did not reach significance for overall or relapse free survival.


CONCLUSIONS
Our results show that although bFGF is elevated in breast carcinomas compared to normal breast tissue it is not related to microvessel density and it is not an independent predictor of survival in breast cancer patients. Basic FGF may be one of multiple factors that synergise with other growth factors such as VEGF to enhance angiogenesis.
Smith
K
K
ICRF Molecular Oncology Laboratory, John Radcliffe Hospital, Oxford, UK. smithk@icrf.icnet.uk
Fox
S B
SB
Whitehouse
R
R
Taylor
M
M
Greenall
M
M
Clarke
J
J
Harris
A L
AL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000098:blood supply / Q000503:physiopathology*; D066246:ErbB Receptors / Q000032:analysis*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000096:biosynthesis* / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis*; D016019:Survival Analysis; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D016222:Fibroblast Growth Factor 2; D066246:ErbB Receptors