Amplification of SKI is a prognostic marker in early colorectal cancer

被引:60
作者
Buess, M
Terracciano, L
Reuter, J
Ballabeni, P
Boulay, JL
Laffer, U
Metzger, U
Herrmann, R
Rochlitz, CF
机构
[1] Univ Basel Hosp, Dept Oncol, CH-4031 Basel, Switzerland
[2] Univ Basel Hosp, Dept Res, CH-4031 Basel, Switzerland
[3] Univ Basel Hosp, Dept Pathol, CH-4031 Basel, Switzerland
[4] Swiss Grp Clin Canc Res, CH-3008 Bern, Switzerland
[5] Spitalzentrum, Dept Surg, CH-2502 Biel, Switzerland
[6] Stadtspital Triemli, Dept Surg, CH-8063 Zurich, Switzerland
来源
NEOPLASIA | 2004年 / 6卷 / 03期
关键词
prognostic; predictive; colorectal cancer; TGF-beta; SMAD;
D O I
10.1593/neo.03442
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND: Improved risk stratification of early colorectal cancer might help to better select patients for adjuvant treatment. Alterations in the transforming growth factor-beta JGF-beta pathway have frequently been found in colorectal cancer, but their impact on prognosis remains controversial. We therefore analyzed two transcriptional corepressors of the TGF-beta 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.
引用
收藏
页码:207 / 212
页数:6
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