c-met tyrosine kinase receptor expression is associated with abnormal beta-catenin expression and favourable prognostic factors in invasive breast carcinoma.
OBJECTIVE
Receptor-type tyrosine kinases are important in cell signal transduction and proliferation. Abnormal expression of tyrosine kinases often leads to malignant transformation. c-met is a tyrosine kinase receptor and its ligand is hepatocyte growth factor (HGF). In this study, we have evaluated c-met expression in 69 invasive breast carcinomas and statistically analysed this expression with known clinicopathological prognostic parameters and patients' survival. We also studied for the first time c-met expression in association with E-cadherin and beta-catenin expression.


RESULTS
Immunohistochemistry (ABC-HRP method) was peformed for the detection of c-met, E-cadherin and beta-catenin. c-met immunoreactivity was observed in 58% of cases and was associated with the lobular type of breast carcinomas (P = 0.012), low histological grade ductal carcinomas (P = 0.05), favourable prognostic and predictive factors such as oestrogen and progesterone receptor immunohistochemical expression and negative c-erbB-2 expression (P = 0.05, P = 0.014 and P = 0.03, respectively). c-met immunoreactivity did not correlate with lymph node status, tumour size and stage of the disease. Cox's proportional hazard regression model demonstrated that tumours with positive c-met immunoreactivity correlated significantly with favourable patients' survival (P = 0.028). When c-met staining was compared with E-cadherin and beta-catenin expression, a statistical significant correlation was established between c-met immunoreactivity and abnormal beta-catenin expression (P = 0.025) suggesting possible involvement of c-met in the downregulation of the E-cadherin-catenin complex, possibly through tyrosine phosphorylation of beta-catenin.


CONCLUSIONS
c-met immunohistochemical expression seems to be associated with abnormal beta-catenin expression, good prognostic and predictive factors and favourable outcome in breast cancer patients.
Nakopoulou
L
L
Departments of Pathology, Gynaecology and Obstetrics, Medical School, University of Athens, Greece. lnakopou@cc.uoa.gr
Gakiopoulou
H
H
Keramopoulos
A
A
Giannopoulou
I
I
Athanassiadou
P
P
Mavrommatis
J
J
Davaris
P S
PS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D019859:Proto-Oncogene Proteins c-met