c-met tyrosine kinase receptor expression is associated with abnormal beta-catenin expression and favourable prognostic factors in invasive breast carcinoma

Histopathology. 2000 Apr;36(4):313-25. doi: 10.1046/j.1365-2559.2000.00847.x.


Aims: 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.

Methods and 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.

Conclusion: 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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Cadherins / metabolism
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / pathology
  • Cytoskeletal Proteins / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Proto-Oncogene Proteins c-met / metabolism*
  • Trans-Activators*
  • beta Catenin


  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • Trans-Activators
  • beta Catenin
  • Proto-Oncogene Proteins c-met