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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.HP

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.

Authors+Show Affiliations

Department of Biological and Environmental Sciences, University of Sannio, 82100 Benevento, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19121846

Citation

Pancione, Massimo, et al. "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." Human Pathology, vol. 40, no. 5, 2009, pp. 714-25.
Pancione M, Forte N, Sabatino L, et al. 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;40(5):714-25.
Pancione, M., Forte, N., Sabatino, L., Tomaselli, E., Parente, D., Febbraro, A., & Colantuoni, V. (2009). 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. Human Pathology, 40(5), 714-25. https://doi.org/10.1016/j.humpath.2008.08.019
Pancione M, et al. 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;40(5):714-25. PubMed PMID: 19121846.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Pancione,Massimo, AU - Forte,Nicola, AU - Sabatino,Lina, AU - Tomaselli,Eugenio, AU - Parente,Domenico, AU - Febbraro,Antonio, AU - Colantuoni,Vittorio, Y1 - 2009/01/03/ PY - 2008/05/30/received PY - 2008/07/31/revised PY - 2008/08/19/accepted PY - 2009/1/6/entrez PY - 2009/1/6/pubmed PY - 2009/6/6/medline SP - 714 EP - 25 JF - Human pathology JO - Hum Pathol VL - 40 IS - 5 N2 - 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. SN - 1532-8392 UR - https://www.unboundmedicine.com/medline/citation/19121846/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0046-8177(08)00509-1 DB - PRIME DP - Unbound Medicine ER -