LEF-1 and TCF4 expression correlate inversely with survival in colorectal cancer

<p>Abstract</p> <p>Background</p> <p>Most colorectal carcinomas are driven by an activation of the canonical Wnt signalling pathway, which promotes the expression of multiple target genes mediating proliferation inavasion and invasion. Upon activation of the Wnt signall...

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Main Authors: Kirchner Thomas, Engel Jutta, Reiche Jana A, Horst David, Kriegl Lydia, Jung Andreas
Format: Article
Language:English
Published: BMC 2010-11-01
Series:Journal of Translational Medicine
Online Access:http://www.translational-medicine.com/content/8/1/123
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author Kirchner Thomas
Engel Jutta
Reiche Jana A
Horst David
Kriegl Lydia
Jung Andreas
author_facet Kirchner Thomas
Engel Jutta
Reiche Jana A
Horst David
Kriegl Lydia
Jung Andreas
author_sort Kirchner Thomas
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Most colorectal carcinomas are driven by an activation of the canonical Wnt signalling pathway, which promotes the expression of multiple target genes mediating proliferation inavasion and invasion. Upon activation of the Wnt signalling pathway its key player β-catenin translocates from the cytoplasm to the nucleus and binds to members of the T-cell factor (TCF)/lymphoid enhancer factor (LEF-1) family namely LEF-1 and TCF4 which are central mediators of transcription. In this study we investigated the expression of β-Catenin, LEF1 and TCF4 in colorectal carcinomas and their prognostic significance.</p> <p>Methods</p> <p>Immunohistochemical analyses of LEF-1, TCF4 and nuclear β-Catenin were done using a tissue microarray with 214 colorectal cancer specimens. The expression patterns were compared with each other and the results were correlated with clinicopathologic variables and overall survival in univariate and multivariate analysis.</p> <p>Results</p> <p>LEF-1 expression was found in 56 (26%) and TCF4 expression in 99 (46%) of colorectal carcinomas and both were heterogenously distributed throughout the tumours. Comparing LEF-1, TCF4 and β-catenin expression patterns we found no correlation. In univariate analysis, TCF4 expression turned out to be a negative prognostic factor being associated with shorter overall survival (p = 0.020), whereas LEF-1 expression as well as a LEF-1/TCF4 ratio were positive prognostic factors and correlated with longer overall survival (p = 0.015 respectively p = 0.001). In multivariate analysis, LEF-1 and TCF4 expression were confirmed to be independent predictors of longer respectively shorter overall survival, when considered together with tumour stage, gender and age (risk ratio for LEF-1: 2.66; p = 0.027 risk ratio for TCF4: 2.18; p = 0.014).</p> <p>Conclusions</p> <p>This study demonstrates different prognostic values of LEF-1 and TCF4 expression in colorectal cancer patients indicating different regulation of these transcription mediators during tumour progression. Moreover both factors may serve as new potential predictive markers in low stage colon cancer cases in advance.</p>
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spelling doaj.art-00cc1ba9b152432784eefc9d271c4c2b2022-12-22T02:08:59ZengBMCJournal of Translational Medicine1479-58762010-11-018112310.1186/1479-5876-8-123LEF-1 and TCF4 expression correlate inversely with survival in colorectal cancerKirchner ThomasEngel JuttaReiche Jana AHorst DavidKriegl LydiaJung Andreas<p>Abstract</p> <p>Background</p> <p>Most colorectal carcinomas are driven by an activation of the canonical Wnt signalling pathway, which promotes the expression of multiple target genes mediating proliferation inavasion and invasion. Upon activation of the Wnt signalling pathway its key player β-catenin translocates from the cytoplasm to the nucleus and binds to members of the T-cell factor (TCF)/lymphoid enhancer factor (LEF-1) family namely LEF-1 and TCF4 which are central mediators of transcription. In this study we investigated the expression of β-Catenin, LEF1 and TCF4 in colorectal carcinomas and their prognostic significance.</p> <p>Methods</p> <p>Immunohistochemical analyses of LEF-1, TCF4 and nuclear β-Catenin were done using a tissue microarray with 214 colorectal cancer specimens. The expression patterns were compared with each other and the results were correlated with clinicopathologic variables and overall survival in univariate and multivariate analysis.</p> <p>Results</p> <p>LEF-1 expression was found in 56 (26%) and TCF4 expression in 99 (46%) of colorectal carcinomas and both were heterogenously distributed throughout the tumours. Comparing LEF-1, TCF4 and β-catenin expression patterns we found no correlation. In univariate analysis, TCF4 expression turned out to be a negative prognostic factor being associated with shorter overall survival (p = 0.020), whereas LEF-1 expression as well as a LEF-1/TCF4 ratio were positive prognostic factors and correlated with longer overall survival (p = 0.015 respectively p = 0.001). In multivariate analysis, LEF-1 and TCF4 expression were confirmed to be independent predictors of longer respectively shorter overall survival, when considered together with tumour stage, gender and age (risk ratio for LEF-1: 2.66; p = 0.027 risk ratio for TCF4: 2.18; p = 0.014).</p> <p>Conclusions</p> <p>This study demonstrates different prognostic values of LEF-1 and TCF4 expression in colorectal cancer patients indicating different regulation of these transcription mediators during tumour progression. Moreover both factors may serve as new potential predictive markers in low stage colon cancer cases in advance.</p>http://www.translational-medicine.com/content/8/1/123
spellingShingle Kirchner Thomas
Engel Jutta
Reiche Jana A
Horst David
Kriegl Lydia
Jung Andreas
LEF-1 and TCF4 expression correlate inversely with survival in colorectal cancer
Journal of Translational Medicine
title LEF-1 and TCF4 expression correlate inversely with survival in colorectal cancer
title_full LEF-1 and TCF4 expression correlate inversely with survival in colorectal cancer
title_fullStr LEF-1 and TCF4 expression correlate inversely with survival in colorectal cancer
title_full_unstemmed LEF-1 and TCF4 expression correlate inversely with survival in colorectal cancer
title_short LEF-1 and TCF4 expression correlate inversely with survival in colorectal cancer
title_sort lef 1 and tcf4 expression correlate inversely with survival in colorectal cancer
url http://www.translational-medicine.com/content/8/1/123
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AT reichejanaa lef1andtcf4expressioncorrelateinverselywithsurvivalincolorectalcancer
AT horstdavid lef1andtcf4expressioncorrelateinverselywithsurvivalincolorectalcancer
AT kriegllydia lef1andtcf4expressioncorrelateinverselywithsurvivalincolorectalcancer
AT jungandreas lef1andtcf4expressioncorrelateinverselywithsurvivalincolorectalcancer