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Nuclear expression of Glycogen synthase kinase‐3β and lack of membranous β‐catenin is correlated with poor survival in colon cancer
Author(s) -
Salim Tavga,
Sjölander Anita,
SandDejmek Janna
Publication year - 2013
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28074
Subject(s) - colorectal cancer , gsk 3 , wnt signaling pathway , tissue microarray , metastasis , immunohistochemistry , catenin , cancer , cancer research , pathology , glycogen synthase , medicine , biology , kinase , signal transduction , glycogen , biochemistry , microbiology and biotechnology
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.