Nuclear expression of Glycogen synthase kinase-3 beta and lack of membranous beta-catenin is correlated with poor survival in colon cancer
(2013) In International Journal of Cancer 133(4). p.807-815- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3920810
- author
- Salim, Tavga LU ; Sjölander, Anita LU and Sand-Dejmek, Janna LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- GSK-3 beta, beta-catenin, colon cancer, metastasis, survival
- in
- International Journal of Cancer
- volume
- 133
- issue
- 4
- pages
- 807 - 815
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000320194400004
- scopus:84878851884
- pmid:23389968
- ISSN
- 0020-7136
- DOI
- 10.1002/ijc.28074
- language
- English
- LU publication?
- yes
- id
- 052b5ffc-0a87-4510-9988-9e7e1330e13c (old id 3920810)
- date added to LUP
- 2016-04-01 09:57:14
- date last changed
- 2022-04-19 21:15:17
@article{052b5ffc-0a87-4510-9988-9e7e1330e13c, abstract = {{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.}}, author = {{Salim, Tavga and Sjölander, Anita and Sand-Dejmek, Janna}}, issn = {{0020-7136}}, keywords = {{GSK-3 beta; beta-catenin; colon cancer; metastasis; survival}}, language = {{eng}}, number = {{4}}, pages = {{807--815}}, publisher = {{John Wiley & Sons Inc.}}, series = {{International Journal of Cancer}}, title = {{Nuclear expression of Glycogen synthase kinase-3 beta and lack of membranous beta-catenin is correlated with poor survival in colon cancer}}, url = {{http://dx.doi.org/10.1002/ijc.28074}}, doi = {{10.1002/ijc.28074}}, volume = {{133}}, year = {{2013}}, }