Nuclear expression of Glycogen synthase kinase-3β and lack of membranous β-catenin is correlated with poor survival in colon cancer

Authors

  • Tavga Salim,

    1. Cell and Experimental Pathology, Department of Laboratory Medicine, Lund University, Skåne University Hospital Malmö, Sweden
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  • Anita Sjölander,

    1. Cell and Experimental Pathology, Department of Laboratory Medicine, Lund University, Skåne University Hospital Malmö, Sweden
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    • Sjölander and sand-Dejmek contributed equally to this work.

  • Janna Sand-Dejmek

    Corresponding author
    1. Section of Surgery, Department of Clinical Sciences, Malmö, Lund University, Skåne University Hospital Malmö, Sweden
    • Cell and Experimental Pathology, Department of Laboratory Medicine, Lund University, Skåne University Hospital Malmö, Sweden
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    • Sjölander and sand-Dejmek contributed equally to this work.


Correspondence to: Dr. Janna Sand-Dejmek, Cell and Experimental Pathology, Clinical Research Center, Jan Waldenströms gata 35, 205 02 Malmö, Sweden, Tel: +4640391154, Fax: +4640391177, E-mail: jannasd@gmail.com

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.

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