c‐met tyrosine kinase receptor expression is associated with abnormal β‐catenin expression and favourable prognostic factors in invasive breast carcinoma
- 1 April 2000
- journal article
- research article
- Published by Wiley in Histopathology
- Vol. 36 (4), 313-325
- https://doi.org/10.1046/j.1365-2559.2000.00847.x
Abstract
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 β-catenin expression. Immunohistochemistry (ABC-HRP method) was peformed for the detection of c-met, E-cadherin and β-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 β-catenin expression, a statistical significant correlation was established between c-met immunoreactivity and abnormal β-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 β-catenin. c-met immunohistochemical expression seems to be associated with abnormal β-catenin expression, good prognostic and predictive factors and favourable outcome in breast cancer patients.Keywords
This publication has 37 references indexed in Scilit:
- Induction of tyrosine phosphorylation and association of β-catenin with EGF receptor upon tryptic digestion of quiescent cells at confluenceOncogene, 1997
- Hepatocyte growth factor/scatter factor expression and c-met in primary breast cancerSurgical Oncology, 1996
- Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasivenessBiochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1994
- Scatter factor/hepatocyte growth factor and its receptor, the c-met tyrosine kinase, can mediate a signal exchange between mesenchyme and epithelia during mouse development.The Journal of cell biology, 1993
- The Met receptor tyrosine kinase transduces motility, proliferation, and morphogenic signals of scatter factor/hepatocyte growth factor in epithelial cells.The Journal of cell biology, 1993
- Loss of epithelial differentiation and gain of invasiveness correlates with tyrosine phosphorylation of the E-cadherin/beta-catenin complex in cells transformed with a temperature-sensitive v-SRC gene.The Journal of cell biology, 1993
- Frequent amplification of the c-met gene in scirrhous type stomach cancerBiochemical and Biophysical Research Communications, 1992
- Hepatocyte growth factorHepatology, 1992
- Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor roleCell, 1991
- Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures.Journal of Histochemistry & Cytochemistry, 1981