BACKGROUND: Improved risk stratification of early colorectal cancer might help to better select patients for adjuvant treatment. Alterations in the transforming growth factor-beta (TGF-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.
RCT Entities:
BACKGROUND: Improved risk stratification of early colorectal cancer might help to better select patients for adjuvant treatment. Alterations in the transforming growth factor-beta (TGF-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.
Authors: J L Boulay; G Mild; J Reuter; M Lagrange; L Terracciano; A Lowy; U Laffer; B Orth; U Metzger; B Stamm; S Martinoli; R Herrmann; C Rochlitz Journal: Genes Chromosomes Cancer Date: 2001-07 Impact factor: 5.006
Authors: C C Compton; L P Fielding; L J Burgart; B Conley; H S Cooper; S R Hamilton; M E Hammond; D E Henson; R V Hutter; R B Nagle; M L Nielsen; D J Sargent; C R Taylor; M Welton; C Willett Journal: Arch Pathol Lab Med Date: 2000-07 Impact factor: 5.534
Authors: Meera Nanjundan; Kwai Wa Cheng; Fan Zhang; John Lahad; Wen-Lin Kuo; Rosemarie Schmandt; Karen Smith-McCune; David Fishman; Joe W Gray; Gordon B Mills Journal: Mol Oncol Date: 2008-05-10 Impact factor: 6.603