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

SummaryRecent studies have reported cross talk between β-catenin, peroxisome proliferator–activated receptor–γ, 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 β-catenin, peroxisome proliferator–activated receptor–γ, cyclooxygenase 2, and nuclear factor κB levels by immunohistochemistry and Western blot. The expression profiles were correlated with patient outcome and 5-year survival. Nuclear β-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–γ expression (70.8%) were significantly associated with a favorable prognosis (P < .001). Remarkably, reduction or loss of β-catenin (22.2%) and peroxisome proliferator–activated receptor–γ (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, β-catenin and peroxisome proliferator–activated receptor–γ levels were inversely correlated with cyclooxygenase 2 (P < .01) and nuclear factor κB expression (P < .05). Our results suggest that reduced expression of β-catenin and peroxisome proliferator–activated receptor–γ 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.