Hepatocyte growth factor/scatter factor (HGF/SF) is a fibroblast-deriv
ed cytokine whose receptor is encoded by c-met. Activation of c-met pr
omotes tumour cell proliferation, dissociation, invasiveness acid angi
ogenesis. Aberrant expression of HGF/SF or c-met may play a role in tu
mour progression. HGF/SF and c-met were determined in 73 breast cancer
s (median follow up: 61 months) and 10 samples of tumour-free-breast t
issue. HGF/SF was detected at significantly higher concentrations in b
reast cancers (median 350, range 58-1604 ng per 100 mg total protein)
when compared with normal breast tissue (median 108, range 66-213 ng p
er 100 mg total protein) (P < 0.001). C-met was detected in all 10 sam
ples of tumour-free breast tissue and in 26 breast cancers. HGF/SF con
centrations correlated with disease relapse (P < 0.001) and reduced ov
erall survival (P < 0.001). Tumours with detectable c-met correlated s
ignificantly with disease-relapse (P = 0.012). Multivariate analysis d
emonstrated a significant interaction between HGF/SF and c-met in rela
tion to disease-relapse (P = 0.014). These results suggest a biologica
l interaction involving HGF/SF and c-met in promoting tumour progressi
on in breast cancer.