Adjuvant chemotherapy reduces the incidence of distant
metastasis and increases survival of patients with
colorectal cancer. However, predictive markers are needed to define subsets of patients with stage II and III disease that may benefit from adjuvant treatment. A secreted member of the
TNF receptor superfamily, the decoy receptor 3 (DcR3), was reported to be amplified in
colorectal cancer as a negative regulator of Fas-mediated apoptosis. We analyzed DcR3 gene copy number and
protein expression in a large series of
tumors from a randomized multicenter trial of
5-fluorouracil/
mitomycin C (FU/MMC)
adjuvant chemotherapy of the Swiss Group for Clinical
Cancer Research (SAKK 40/81), using real-time quantitative PCR and immunohistochemistry on
tumor microarrays. Results of gene status and
protein expression of DcR3 were correlated with disease-free and overall survival of patients. We observed amplification of the DcR3 gene in 185/294 (63%) and overexpression of the DcR3
protein in 163/223 (73%) of
colorectal tumors. Multivariate analysis showed no prognostic effect of DcR3 gene amplification and
protein overexpression. However,
adjuvant chemotherapy was significantly more beneficial in patients with normal DcR3 gene copy number than in patients with amplification (DFS: HR 2.84, 95% CI 1.16-6.98, p = 0.02; OS: HR 3.15, 95% CI 1.19-8.32, p = 0.02), whereas DcR3
protein overexpression did not influence the effect of
adjuvant chemotherapy (DFS: HR 1.02, 95% CI 0.65-1.60, p = 0.95; OS: HR 0.95, 95% CI 0.61-1.49, p = 0.83). We conclude that amplification of the 20q13 locus is a predictive marker for
adjuvant chemotherapy in
colorectal cancer.