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

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Author

Summary, in English

Dysregulation of Wnt/beta-catenin signaling is a hallmark of colon cancer. Glycogen synthase kinase-3 beta (GSK-3 beta) 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-3 beta in colon cancer. A tumor tissue microarray of primary colon cancers and metastases was used to evaluate expression and subcellular localization of GSK-3 beta and beta-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-3 beta in 39% (33/85) of evaluated tumors. Nuclear GSK-3 beta 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 beta-catenin (p=0.007). Loss of membranous beta-catenin occurred in 37% (30/82) of the tumors and was associated with poor survival (p=0.016). The combination of nuclear GSK-3 beta and lack of membrane beta-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-3 beta and loss of membrane beta-catenin identify a subset of colon carcinomas with worse prognosis.

Department/s

Publishing year

2013

Language

English

Pages

807-815

Publication/Series

International Journal of Cancer

Volume

133

Issue

4

Document type

Journal article

Publisher

John Wiley & Sons Inc.

Topic

  • Cancer and Oncology

Keywords

  • GSK-3 beta
  • beta-catenin
  • colon cancer
  • metastasis
  • survival

Status

Published

Research group

  • Cell Pathology, Malmö
  • Surgery

ISBN/ISSN/Other

  • ISSN: 0020-7136