Significance of E-cadherin/beta-catenin complex and cyclin D1 in breast cancer

Oncol Rep. 2002 Sep-Oct;9(5):915-28.

Abstract

E-cadherin and beta-catenin are important epithelial adhesion molecules in normal epithelium. Loss of E-cadherin - beta-catenin adhesion is an important step in the progression of many epithelial malignancies. beta-catenin plays also a role in intracellular signaling and can function as an oncogene when binds to the T-cell factor 4 (Tcf4)-binding site in the promotor region of cyclin D1 and transactivates genes after translocation to the nucleus. We evaluated the immunohistochemical expression pattern of E-cadherin, beta-catenin in relationship with cyclin D1 overexpression, tumor stage, clinicopathologic parameters and patient survival in 128 mammary infiltrating duct carcinomas. The expression of E-cadherin/beta-catenin complex and beta-catenin/cyclin D1 double staining with confocal scanning laser microscope was evaluated. There were aberrant expressions in 78% of E-cadherin, 79% of beta-catenin, and 66% of cyclin D1 in breast cancer. There was correlation of aberrant expression of E-cadherin or beta-catenin with lymph node metastasis, survival rate, and survival length. However, there was no correlation of cyclin D1 overexpression with aberrant expression of E-cadherin or beta-catenin. No death was found in normal expression of beta-catenin, however lowest survival (50%) was found in nuclear beta-catenin expression. There was correlation of overexpression of cyclin D1 with survival rate and survival length. The highest survival rate and survival length were found in membranous normal beta-catenin expression group, however significant decrement of survival length was found in the groups of aberrant expression one or both of E-cadherin or/and beta-catenin. These results suggest that aberrant expression of E-cadherin, beta-catenin, and cyclin D1 may be involved in tumor metastasis, and analysis of the degree or the pattern of E-cadherin, beta-catenin, cyclin D1, and E-cadherin/beta-catenin complex may be good prognostic markers of mammary infiltrating duct carcinoma.

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / metabolism*
  • Cadherins / biosynthesis*
  • Carcinoma, Ductal, Breast / diagnosis
  • Carcinoma, Ductal, Breast / metabolism*
  • Cyclin D1 / biosynthesis*
  • Cytoskeletal Proteins / biosynthesis*
  • Female
  • Humans
  • Immunohistochemistry
  • Microscopy, Fluorescence
  • Middle Aged
  • Prognosis
  • Time Factors
  • Trans-Activators / biosynthesis*
  • Treatment Outcome
  • beta Catenin

Substances

  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • Trans-Activators
  • beta Catenin
  • Cyclin D1