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-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.


CONCLUSIONS
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.
Buess
Martin
M
Departments of Oncology and Research, University Hospital of Basel, Basel CH-4031, Switzerland.
Terracciano
Luigi
L
Reuter
Jürgen
J
Ballabeni
Pierluigi
P
Boulay
Jean-Louis
JL
Laffer
Urban
U
Metzger
Urs
U
Herrmann
Richard
R
Rochlitz
Christoph
C
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D042241:Early Diagnosis; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C060614:SKI protein, human