Oncogenic beta-catenin and MMP-7 (matrilysin) cosegregate in late-stage clinical colon cancer

Gastroenterology. 2002 Jan;122(1):60-71. doi: 10.1053/gast.2002.30306.


Background & aims: Recent in vitro studies showed that beta-catenin translocated into the tumor cell nucleus functions as an oncogene by transactivating oncogenes, including MMP-7. We conducted a large-scale analysis of beta-catenin and MMP-7 expression in human colon cancer to determine the potential clinical importance of these molecules.

Methods: In 202 colon cancer patients with known postoperative outcomes, we determined the expression of beta-catenin and MMP-7 in the tumors immunohistochemically and correlated the findings with the patients' clinicopathological characteristics and survival.

Results: We found 2 distinct patterns of beta-catenin nuclear accumulation (NA) in the colon cancers: diffuse NA (NAd) in 89 cases (44%) and selective NA at the invasion front (NAinv) in 18 cases (9%). The presence of the NAinv pattern was significantly correlated with advanced Dukes' stage (P = 0.0187) and tumor recurrence (P = 0.0005) as well as with MMP-7 expression in the tumor invasion front (P = 0.0025), resulting in extremely unfavorable clinical outcomes. A multivariate analysis determined that the NAinv expression pattern and Dukes' C stage were independent prognostic factors.

Conclusions: Oncogenic activation of beta-catenin in the tumor invasion front, as represented by its NAinv pattern of expression, may be an independent and reliable indicator of membership in a subset of colon cancer patients who are highly susceptible to tumor recurrence and have a less favorable survival rate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / mortality
  • Colonic Neoplasms / pathology
  • Cytoskeletal Proteins / analysis
  • Cytoskeletal Proteins / biosynthesis*
  • Female
  • Genes, ras / genetics
  • Humans
  • Immunohistochemistry
  • Male
  • Matrix Metalloproteinase 7 / analysis
  • Matrix Metalloproteinase 7 / biosynthesis*
  • Middle Aged
  • Mutation
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prognosis
  • Survival Analysis
  • Trans-Activators*
  • beta Catenin


  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Trans-Activators
  • beta Catenin
  • Matrix Metalloproteinase 7