Amplification of SKI Is a Prognostic Marker in Early Colorectal Cancer

BACKGROUND: Improved risk stratification of early colorectal cancer might help to better select patients for adjuvant treatment. Alterations in the transforming growth factor-β (TGIF-β) pathway have frequently been found in colorectal cancer, but their impact on prognosis remains controversial. We t...

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Bibliographic Details
Main Authors: Martin Buess, Luigi Terracciano, Jürgen Reuter, Pierluigi Ballabeni, Jean-Louis Boulay, Urban Laffer, Urs Metzger, Richard Herrmann, Christoph F. Rochlitz
Format: Article
Language:English
Published: Elsevier 2004-05-01
Series:Neoplasia: An International Journal for Oncology Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S1476558604800678
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Summary:BACKGROUND: Improved risk stratification of early colorectal cancer might help to better select patients for adjuvant treatment. Alterations in the transforming growth factor-β (TGIF-β) pathway have frequently been found in colorectal cancer, but their impact on prognosis remains controversial. We therefore analyzed two transcriptional corepressors of the TGF-β signaling pathway with respect to prognosis and prediction of chemotherapy benefit in early colorectal cancer. METHODS: The gene copy status of SKI and SNON was analyzed by use of quantitative real-time polymerase chain reaction in 179 colorectal tumor biopsies, which had been collected from a randomized multicenter trial of the Swiss Group for Clinical Cancer Research (SAKK). RESULTS: Partial or complete allelic loss was found in 41.5% and 55.2% for SKI and SNON, whereas amplification was found in 10.1% and 15.1%, respectively. Multivariate Cox analysis showed that gene amplification of SKI independently predicted reduced relapse-free [hazard ratio (HR) for relapse 2.08, P = .049] and overall survival (HR for death 2.62, P =.012). In contrast, deletion of SKI and the gene copy status of SNON were not significantly correlated with prognosis. CONCLUSION: Amplification of SKI is a negative prognostic marker in early-stage colorectal cancer. This marker should help to improve risk stratification to better select patients for adjuvant therapy. Confirmatory investigations are warranted.
ISSN:1476-5586
1522-8002