Tissue microarray analysis of beta-catenin in colorectal cancer shows nuclear phospho-beta-catenin is associated with a better prognosis

Clin Cancer Res. 2001 Dec;7(12):4013-20.


Purpose: Beta-catenin is involved in homotypic cell-cell adhesion and the wnt signaling pathway. Deregulation of beta-catenin levels, caused in part by mutations of the adenomatous polyposis coli gene, is thought to play a role in the development of colorectal and other cancers. To further elucidate their roles, the expression pattern of beta-catenin and phosphospecific beta-catenin was correlated with clinical outcome in a series of patients with colorectal cancer.

Experimental design: Immunohistochemical analysis of a tissue microarray with 650 colorectal cancer specimens was performed to study the expression and subcellular localization of beta-catenin and phosphospecific beta-catenin. These results were correlated with other clinicopathological factors and with overall survival.

Results: The majority of cancers retained some degree of beta-catenin membranous staining, whereas cytoplasmic or nuclear expression was seen in 42.5% and 20.4% of specimens, respectively. Phospho-beta-catenin showed nuclear staining in 9.5% of specimens, and there was no apparent membranous or cytoplasmic staining. There was no significant association between beta-catenin or phospho-beta-catenin and grade or stage. However, there was a positive correlation between beta-catenin and phospho-beta-catenin (P = 0.039), with phospho-beta-catenin representing a subset of nuclear beta-catenin. Patients with nuclear expression of beta-catenin did not have an altered survival compared with those that did not (P = 0.5611). Nuclear expression of phospho-beta-catenin, however, was associated with an improved survival (P = 0.0006). In multivariate analysis, only stage and phospho-beta-catenin were independently predictive of overall survival (P < 0.001 and P = 0.0034, respectively).

Conclusions: These findings support a role for beta-catenin overexpression in colorectal tumorigenesis and provide initial evidence that phospho-beta-catenin may be a marker for improved overall survival independent of stage and grade.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cadherins / analysis
  • Cell Line
  • Cell Nucleus / pathology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Cytoplasm / pathology
  • Cytoskeletal Proteins / analysis
  • Cytoskeletal Proteins / genetics*
  • Dogs
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Neoplasm Staging
  • Oligonucleotide Array Sequence Analysis*
  • Phosphoproteins / analysis*
  • Prognosis
  • Proportional Hazards Models
  • Recombinant Proteins / analysis
  • Reproducibility of Results
  • Survival Rate
  • Trans-Activators*
  • Transfection
  • Treatment Outcome
  • beta Catenin


  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • Phosphoproteins
  • Recombinant Proteins
  • Trans-Activators
  • beta Catenin