Reduced beta-catenin and peroxisome proliferator-activated receptor-gamma expression levels are associated with colorectal cancer metastatic progression: correlation with tumor-associated macrophages, cyclooxygenase 2, and patient outcome

Hum Pathol. 2009 May;40(5):714-25. doi: 10.1016/j.humpath.2008.08.019. Epub 2009 Jan 3.

Abstract

Recent studies have reported cross talk between beta-catenin, peroxisome proliferator-activated receptor-gamma, and cyclooxygenase 2 signaling pathways. We examined whether molecular changes of these pathways could be related to colorectal cancer metastatic progression. Seventy-two sporadic colorectal cancers and the distant nonneoplastic mucosa were analyzed for beta-catenin, peroxisome proliferator-activated receptor-gamma, cyclooxygenase 2, and nuclear factor kappaB levels by immunohistochemistry and Western blot. The expression profiles were correlated with patient outcome and 5-year survival. Nuclear beta-catenin staining was detected in only 18.1% of tumors and correlated with poor survival as compared with cases showing cytosolic/membrane accumulation (59.7%, P < .05). This latter group and tumor samples showing cytosolic/nuclear peroxisome proliferator-activated receptor-gamma expression (70.8%) were significantly associated with a favorable prognosis (P < .001). Remarkably, reduction or loss of beta-catenin (22.2%) and peroxisome proliferator-activated receptor-gamma (29.2%) expression was strongly correlated with marked infiltration of tumor-associated macrophages (P < .01), presence of liver metastases, and very short survival (P = .0001). Moreover, beta-catenin and peroxisome proliferator-activated receptor-gamma levels were inversely correlated with cyclooxygenase 2 (P < .01) and nuclear factor kappaB expression (P < .05). Our results suggest that reduced expression of beta-catenin and peroxisome proliferator-activated receptor-gamma could play a key role in aggressive colorectal cancer behavior. This finding may provide a relevant prognostic tool and contribute to early identification of patients at high risk of mortality.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Aged
  • Biomarkers, Tumor / analysis
  • Blotting, Western
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Cyclooxygenase 2 / metabolism*
  • Disease Progression
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Macrophages / immunology*
  • Male
  • NF-kappa B / biosynthesis
  • Neoplasm Metastasis / pathology
  • Neoplasm Staging
  • PPAR gamma / biosynthesis*
  • Prognosis
  • beta Catenin / biosynthesis*

Substances

  • Biomarkers, Tumor
  • NF-kappa B
  • PPAR gamma
  • beta Catenin
  • Cyclooxygenase 2