Hepatocyte growth factor/scatter factor expression and c-met in primary breast cancer.
Hepatocyte growth factor/scatter factor (HGF/SF) is a fibroblast-derived cytokine whose receptor is encoded by c-met. Activation of c-met promotes tumour cell proliferation, dissociation, invasiveness and angiogenesis. Aberrant expression of HGF/SF or c-met may play a role in tumour progression. HGF/SF and c-met were determined in 73 breast cancers (median follow up: 61 months) and 10 samples of tumour-free breast tissue. HGF/SF was detected at significantly higher concentrations in breast cancers (median 350, range 58-1604 ng per 100 mg total protein) when compared with normal breast tissue (median 108, range 66-213 ng per 100 mg total protein) (P < 0.001). C-met was detected in all 10 samples of tumour-free breast tissue and in 26 breast cancers. HGF/SF concentrations correlated with disease relapse (P < 0.001) and reduced overall survival (P < 0.001). Tumours with detectable c-met correlated significantly with disease-relapse (P = 0.012). Multivariate analysis demonstrated a significant interaction between HGF/SF and c-met in relation to disease-relapse (P = 0.014). These results suggest a biological interaction involving HGF/SF and c-met in promoting tumour progression in breast cancer.
Nagy
J
J
University Department of Surgery, Western Infirmary, Glasgow, UK.
Curry
G W
GW
Hillan
K J
KJ
McKay
I C
IC
Mallon
E
E
Purushotham
A D
AD
George
W D
WD
D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002455:Cell Division; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D009389:Neovascularization, Pathologic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019859:Proto-Oncogene Proteins c-met; D011519:Proto-Oncogenes / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D015996:Survival Rate
D011518:Proto-Oncogene Proteins; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases