Beta-catenin in soft tissue sarcomas: expression is related to proliferative activity in high-grade sarcomas

Mod Pathol. 2000 Sep;13(9):1005-13. doi: 10.1038/modpathol.3880181.

Abstract

Besides its role in cell adhesion, beta-catenin exerts a function as an oncoprotein. The aim of this study was the characterization of its expression, possible mutation, and the assessment of beta-catenin as a prognostic indicator for soft tissue sarcomas. A total of 115 soft tissue sarcomas were analyzed using immunohistochemistry, immunogold-electron microscopy, and DNA analysis. Information from 56 patients was available for follow-up. A statistically significant correlation was found between intracellular distribution of beta-catenin and the proliferative activity (MIB-1 expression) in high-grade sarcomas (P = .0008). Beta-catenin was identified with intracytoplasmic and nuclear accumulation, showing additional membranous staining in sarcomas with epithelioid pattern. Ultrastructurally, a colocalization between beta-catenin and nuclear heterochromatin was demonstrated. In 22 analyzed tumors, only one (yet undescribed) mutation of the beta-catenin gene (C-A transversion) could be detected. Prognostic validity of the cellular expression of beta-catenin, however, was not proven. Apart from its membranous function as an effective molecule for cell-adhesion in sarcomas with epithelioid pattern, beta-catenin may act as an oncoprotein in sarcomas with intracytoplasmic and nuclear localization with binding to nuclear DNA. A previously discussed stimulation of cell proliferation caused by an increased beta-catenin level can also be postulated for high-grade soft tissue sarcomas in correlation with the rate of proliferation. Mutations of the beta-catenin gene are probably of lesser importance for the accumulation of beta-catenin in soft tissue sarcomas.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Nuclear
  • Base Sequence
  • Cell Division
  • Cell Nucleus / chemistry
  • Cell Nucleus / metabolism
  • Cell Nucleus / pathology
  • Cytoskeletal Proteins / analysis
  • Cytoskeletal Proteins / metabolism*
  • Cytosol / chemistry
  • Cytosol / metabolism
  • Cytosol / pathology
  • DNA Mutational Analysis
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Gold
  • Humans
  • Ki-67 Antigen / analysis
  • Male
  • Microscopy, Immunoelectron
  • Middle Aged
  • Molecular Sequence Data
  • Neoplasm Staging
  • Nuclear Proteins / analysis
  • Nuclear Proteins / metabolism
  • Prognosis
  • Sarcoma / chemistry
  • Sarcoma / genetics
  • Sarcoma / metabolism*
  • Sarcoma / pathology
  • Soft Tissue Neoplasms / chemistry
  • Soft Tissue Neoplasms / genetics
  • Soft Tissue Neoplasms / metabolism*
  • Soft Tissue Neoplasms / pathology
  • Staining and Labeling
  • Trans-Activators*
  • beta Catenin

Substances

  • Antigens, Nuclear
  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Ki-67 Antigen
  • Nuclear Proteins
  • Trans-Activators
  • beta Catenin
  • Gold