title: Nuclear expression of glycogen synthase kinase-3β and lack of membranous β-catenin is correlated with poor survival in colon cancer.
abstract: Dysregulation of Wnt/β-catenin signaling is a hallmark of colon cancer. Glycogen synthase kinase-3β (GSK-3β) can be a positive regulator of survival and proliferation of cultured colon cancer cell but its role in clinical colon cancer is unknown. Our objectives were to evaluate the role of GSK-3β in colon cancer. A tumor tissue microarray of primary colon cancers and metastases was used to evaluate expression and subcellular localization of GSK-3β and β-catenin. In total, 85 primary colon cancer samples were evaluated by immunohistochemistry. Immunoreactivity was correlated to known markers of adverse prognosis. Overall survival was the primary end-point. We found nuclear accumulation of GSK-3β in 39% (33/85) of evaluated tumors. Nuclear GSK-3β was significantly associated with shorter overall survival (p = 0.008), larger tumor size (p = 0.015), distant metastasis (p = 0.029) and loss of membranous β-catenin (p = 0.007). Loss of membranous β-catenin occurred in 37% (30/82) of the tumors and was associated with poor survival (p = 0.016). The combination of nuclear GSK-3β and lack of membrane β-catenin occurred in a total of 26% of the studied tumors (21/61) and was significantly and independently associated with poor prognosis. Our results suggest that nuclear expression of GSK-3β and loss of membrane β-catenin identify a subset of colon carcinomas with worse prognosis.
authors: Cell and Experimental Pathology, Department of Laboratory Medicine, Lund University, Skåne University Hospital Malmö, Sweden.
authors: Tavga
authors: T
authors: Salim
authors: Anita
authors: A
authors: Sjölander
authors: Janna
authors: J
authors: Sand-Dejmek
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000201:enzymology*; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007120:Immunochemistry; D008297:Male; D011379:Prognosis; D013347:Subcellular Fractions / Q000201:enzymology / Q000378:metabolism; D016019:Survival Analysis; D046888:Tissue Array Analysis; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3