Prospective multicenter registration study of colorectal cancer: significant variations in radicality and oncosurgical quality-Swiss Group for Clinical Cancer Research Protocol SAKK 40/00.

PURPOSE: This study aimed to investigate in a multicenter cohort study the radicality of colorectal cancer resections, to assess the oncosurgical quality of colorectal specimens, and to compare the performance between centers. METHODS: One German and nine Swiss hospitals agreed to prospectively register all patients with primary colorectal cancer resected between September 2001 and June 2005. The median number of eligible patients with one primary tumor included per center was 95 (range 12-204). RESULTS: The following variations of median values or percentages between centers were found: length of bowel specimen 20-39 cm (25.8 cm), maximum height of mesocolon 6.5-12.5 cm (9.0 cm), number of examined lymph nodes 9-24 (16), distance to nearer bowel resection margin in colon cancer 4.8-12 cm (7 cm), and in rectal cancer 2-3 cm (2.5 cm), central ligation of major artery 40-97 % (71 %), blood loss 200-500 ml (300 ml), need for perioperative blood transfusion 5-40 % (19 %), tumor opened during mobilization 0-11 % (5 %), T4-tumors not en-bloc resected 0-33 % (4 %), inadvertent perforation of mesocolon/mesorectum 0-8 % (4 %), no-touch isolation technique 36-86 % (67 %), abdominoperineal resection for rectal cancer 0-30 % (17 %), rectal cancer specimen with circumferential margin ≤1 mm 0-19 % (10 %), in-hospital mortality 0-6 % (2 %), anastomotic leak or intra-abdominal abscess 0-17 % (7 %), re-operation 0-17 % (8 %). CONCLUSION: In colorectal cancer, surgery considerable variations between different centers were found with regard to radicality and oncosurgical quality, suggesting a potential for targeted improvement of surgical technique.

In-hospital delay increases the risk of perforation in adults with appendicitis.

BACKGROUND: The influence of in-hospital delay (time between admission and operation) on outcome after appendectomy is controversial. METHODS: A total of 1,827 adult patients underwent open or laparoscopic appendectomy for suspected appendicitis in eleven Swiss hospitals between 2003 and 2006. Of these, 1,675 patients with confirmed appendicitis were included in the study. Groups were defined according in-hospital delay (≤12 vs. >12 h). RESULTS: Delay>12 h was associated with a significantly higher frequency of perforated appendicitis (29.7 vs. 22.7%; P=0.010) whereas a delay of 6 or 9 h was not. Size of institution, time of admission, and surgical technique (laparoscopic vs. open) were independent factors influencing in-hospital delay. Admission during regular hours was associated with higher age, higher frequency of co-morbidity, and higher perforation rate compared to admission after hours. The logistic regression identified four independent factors associated with an increased perforation rate: age (≤65 years vs. >65 years, odds ratio (OR) 4.5, P<0.001); co-morbidity (Charlson index>0 vs. Charlson index=0, OR 2.3, P<0.001); time of admission (after hours vs. regular hours, OR 0.8, P=0.040), in-hospital delay (>12 vs. ≤12 h, OR 1.5, P=0.005). Perforation was associated with an increased reintervention rate (13.4 vs. 1.6%; P<0.001) and longer length of hospital stay (9.5 vs. 4.4 days; P<0.001). CONCLUSIONS: In-hospital delay negatively influences outcome after appendectomy. In-hospital delay of more than 12 h, age over 65 years, time of admission during regular hours, and the presence of co-morbidity are all independent risk factors for perforation. Perforation was associated with a higher reintervention rate and increased length of hospital stay.

Protein expression of cancer testis antigens predicts tumor recurrence and treatment response to imatinib in gastrointestinal stromal tumors.

Cancer testis antigens (CTAs) have been identified in various tumors as immunological tumor targets. In gastrointestinal stromal tumor (GIST), the prediction of malignant potential remains difficult but is crucial in the era of adjuvant imatinib treatment. Here, we analyzed the impact of CTAs on tumor recurrence and its role on the treatment response to imatinib. The expression of the most frequent CTAs MAGE-A1, MAGE-A3, MAGE-A4, MAGE-C1 and NY-ESO-1 was analyzed by immunohistochemistry. The duration between the initial operation and the tumor relapse was defined as recurrence free survival (RFS). All recurrent cases were treated with imatinib. The tumor response to imatinib was graded according to the modified CT response evaluation criteria. Patients with a CTA positive GIST (n = 23, 27%) had a significantly shorter RFS (p = 0.001) compared to negative cases (n = 63, 73%). The median RFS was 25 months in CTA positive patients and was not reached during the study period in CTA negative patients. According to the established staging criteria CTA positive tumors were predominantly high-risk tumors (p = 0.001). The expression of MAGE-A3 (p = 0.018) and NY-ESO-1 (p = 0.001) were associated with tumor progression under imatinib treatment. A tendency for worse tumor response to imatinib was observed in CTA positive tumors (p = 0.056). Our study confirms the expression of CTAs in GIST and their role as prognostic markers. It also draws attention to the potential impact of CTAs on the tumor response to imatinib.

Endosonographic radial tumor thickness after neoadjuvant chemoradiation therapy to predict response and survival in patients with locally advanced esophageal cancer: a prospective multicenter phase ll study by the Swiss Group for Clinical Cancer Research (SAKK 75/02).

BACKGROUND: EUS response assessment in patients with locally advanced esophageal cancer undergoing neoadjuvant chemoradiation therapy (CRT) is limited by disintegration of the involved anatomic structures. OBJECTIVE: Predictive and prognostic values of a prospectively defined maximum tumor thickness (MTT). DESIGN: Prospective open-label phase ll study (SAKK 75/02). SETTING: Multicenter, nationwide. PATIENTS: Of 66 patients with primary CRT, 56 underwent en bloc esophagectomy. INTERVENTIONS: EUS-measured MTT before and 2-5 weeks after CRT (yMTT). MAIN OUTCOME MEASUREMENTS: Cutoffs: (1) absolute thickness (yMTT) after CRT < or = 6 mm; (2) relative reduction compared with baseline (ratio yMTT/MTT) < or = 50%. Correlation between EUS measurements and histopathologic tumor regression grade (TRG) and overall survival (OS). RESULTS: Sixteen of 56 patients were not included for EUS evaluation (10 severe stenosis, 5 MTT not measured, 1 intolerance to second EUS). Characteristics (n = 40) were as follow: median age, 60 years; squamous cell carcinoma, 42%; and adenocarcinoma (AC), 58%. Initial stage was: 10 T2N1, 3 T3N0, 26 T3N1, 1 T3Nx; 14 of 23 AC Siewert type 1. Wilcoxon rank sum test showed significant correlation of TRG1 with yMTT < or = 6 mm (P = .008) and yMTT/MTT < or = 50% (P = .003). The effect of yMTT on TRG1 was significant (P = .0193; odds ratio, 0.687 [95% CI, 0.502-0.941]). The predefined cutoff of < or = 6 mm for yMTT was predictive for TRG1 (P = .0037; Fisher exact test). After a median follow-up of 28.6 months, there was a clear trend for benefit in OS with yMTT < or = 6 mm and yMTT/MTT < or = 50%. LIMITATIONS: Small sample size. CONCLUSION: In a multicenter setting, MTT measured by EUS after CRT was highly predictive for response and showed a clear trend for predicting survival.

Use of severity classification systems in the surgical decision-making process in emergency laparotomy for perforated diverticulitis.

PURPOSE: Hartman's procedure (HP) or primary anastomosis (PA) are the two surgical techniques used in patients undergoing emergency colectomy for perforated diverticulitis. There are no objective criteria to guide the surgeon's choice of procedure. This study assesses whether classification and scoring systems can be used in the decision-making process. METHODS: One hundred eleven patients undergoing emergency laparotomy for perforated diverticulitis were analyzed. Logistic regression and interaction models were used to determine the predictive value in the two settings. RESULTS: Sixty five patients underwent HP and 46 patients underwent PA. Patients with HP had significantly higher scores, median age, and were more often on immunosuppressive medication. Mortality and surgical morbidity did not differ between the groups. The clinical anastomotic leak rate was 28.3% in the PA group. In the univariate logistic regression for in-hospital death, all scores showed a significant influence. The multivariate logistic regression analysis showed that only Charlson comorbidity index (CCI) and American Society of Anesthesiologists score had a significant influence on mortality. Each score was analyzed for its predictive value regarding mortality and morbidity with respect to type of operative procedure. Only CCI revealed a trend towards statistical significance. The risk of death increases with increasing CCI when PA is performed compared to HP. CONCLUSION: None of the tested scores can be used to help the surgeon decide whether a PA or HP is appropriate in a specific patient. Comorbidity, represented as CCI in this study, might be more important than the locoregional situation.

Lack of extended venous thromboembolism prophylaxis in high-risk patients undergoing major orthopaedic or major cancer surgery. Electronic Assessment of VTE Prophylaxis in High-Risk Surgical Patients at Discharge from Swiss Hospitals (ESSENTIAL).

Extended pharmacological venous thromboembolism (VTE) prophylaxis beyond discharge is recommended for patients undergoing high-risk surgery. We prospectively investigated prophylaxis in 1,046 consecutive patients undergoing major orthopaedic (70%) or major cancer surgery (30%) in 14 Swiss hospitals. Appropriate in-hospital prophylaxis was used in 1,003 (96%) patients. At discharge, 638 (61%) patients received prescription for extended pharmacological prophylaxis: 564 (77%) after orthopaedic surgery, and 74 (23%) after cancer surgery (p < 0.001). Patients with knee replacement (94%), hip replacement (81%), major trauma (80%), and curative arthroscopy (73%) had the highest prescription rates for extended VTE prophylaxis; the lowest rates were found in patients undergoing major surgery for thoracic (7%), gastrointestinal (19%), and hepatobiliary (33%) cancer. The median duration of prescribed extended prophylaxis was longer in patients with orthopaedic surgery (32 days, interquartile range 14-40 days) than in patients with cancer surgery (23 days, interquartile range 11-30 days; p<0.001). Among the 278 patients with an extended prophylaxis order after hip replacement, knee replacement, or hip fracture surgery, 120 (43%) received a prescription for at least 35 days, and among the 74 patients with an extended prophylaxis order after major cancer surgery, 20 (27%) received a prescription for at least 28 days. In conclusion, approximately one quarter of the patients with major orthopaedic surgery and more than three quarters of the patients with major cancer surgery did not receive prescription for extended VTE prophylaxis. Future effort should focus on the improvement of extended VTE prophylaxis, particularly in patients undergoing major cancer surgery.

Influence of thoracic epidural analgesia on postoperative pain relief and ileus after laparoscopic colorectal resection : Benefit with epidural analgesia.

BACKGROUND: Thoracic epidural analgesia (TEA) provides superior analgesia with a lower incidence of postoperative ileus when compared with systemic opiate analgesia in open colorectal surgery. However, in laparoscopic colorectal surgery the role of TEA is not well defined. This prospective observational study investigates the influence of TEA in laparoscopic colorectal resections. METHODS: All patients undergoing colorectal resection between November 2004 and February 2007 were assessed for inclusion into a prospective randomized trial investigating the influence of bisacodyl on postoperative ileus. All patients treated by laparoscopic resection from this collective were eligible for the present study. Primary endpoints were use of analgesics and visual analogue scale (VAS) pain scores. Secondary endpoint concerned full gastrointestinal recovery, defined as the mean time to the occurrence of the following three events (GI-3): first flatus passed, first defecation, and first solid food tolerated. RESULTS: 75 patients underwent laparoscopic colorectal resection, 39 in the TEA group and 36 in the non-TEA group. Patients with TEA required significantly less analgesics (metamizol median 3.0 g [0-32 g] versus 13.8 g [0-28 g] (p < 0.001); opioids mean 12 mg [+/-2.8 mg standard error of mean, SEM] versus 103 mg [+/-18.2 mg SEM] (p < 0.001). VAS scores were significantly lower in the TEA group (overall mean 1.67 [+/- 0.2 SEM] versus 2.58 [+/-0.2 SEM]; p = 0.004). Mean time to gastrointestinal recovery (GI-3) was significantly shorter (2.96 [+/-0.2 SEM] days versus 3.81 [+/-0.3 SEM] days; p = 0.025). Analysis of the subgroup of patients with laparoscopically completed resections showed corresponding results. CONCLUSION: TEA provides a significant benefit in terms of less analgesic consumption, better postoperative pain relief, and faster recovery of gastrointestinal function in patients undergoing laparoscopic colorectal resection.

Early vs. delayed elective laparoscopic-assisted colectomy in sigmoid diverticulitis: timing of surgery in relation to the acute attack.

PURPOSE: The timing of elective surgery in acute sigmoid diverticulitis in relation to the acute attack is not clear. Early elective surgery during the same hospitalization as the acute attack or delayed surgery after an interval of several weeks are the options. This study was designed to evaluate the influence of timing on morbidity, conversion rate, histologic findings, and costs. METHODS: A total of 178 patients with elective laparoscopic-assisted sigmoid resections for diverticulitis between 1997 and 2005 were retrospectively assessed; 77 patients underwent early and 101 delayed surgery. Outcomes were surgical morbidity, conversion rate, histologic findings, and financial impact of timing. RESULTS: The two groups showed no significant difference apart from a higher body mass index in the delayed group (25.5 vs. 26.6 kg/m2, P = 0.035). Surgical morbidity was not significantly different. Conversion rate was significantly higher in the early group (P < 0.001). Converted patients had an increased surgical morbidity of 23.8 vs. 19.1 percent (P = 0.323) and hospitalization was significantly longer (13.5 vs. 10.5 days; P < 0.001). Histology revealed inflammation in 75.3 percent in the early group compared with 23.8 percent in the delayed group. Total treatment costs were not different between groups, whereas total earnings were higher in the delayed group resulting in a lower hospital deficit. CONCLUSIONS: Early elective surgery in patients with acute sigmoid diverticulitis results in a higher conversion rate. If patients respond to initial antibiotic therapy, delayed colectomy after an interval of six weeks or more is recommended.

The influence of the surgeon's and the hospital's caseload on survival and local recurrence after colorectal cancer surgery.

BACKGROUND: Past studies have identified surgeon- and institution- related characteristics as prognostic factors in colorectal cancer surgery. The present work assesses the influence of the surgeon's and the hospital's caseload on long-term results of colorectal cancer surgery. METHODS: The data on 2706 patients from 2, randomized, colorectal cancer trials (Swiss Group for Clinical Cancer Research [SAKK] 40/81, SAKK 40/87) investigating adjuvant intraportal and systemic chemotherapy and 1 concurrent registration study (SAKK 40/88) were reviewed. A first analysis included 1809 eligible, nonmetastatic patients from all 3 studies. A subsequent subgroup analysis included 915 eligible patients from both randomized trials. Overall survival (OS), disease-free survival (DFS), and local recurrence (LR) were analyzed in multivariate models taking into account the possible effect of clustering. The main potential covariates were surgeon's annual caseload (>5 operations/year vs < or =5 operations/year), hospital's annual caseload (>26 operations/year vs < or =26 operations/year), tumor site, T stage, and nodal status. RESULTS: Primary analysis of all 3 studies combined found a high surgeon's caseload to be positively associated with OS (P = .025) and marginally with DFS (P = .058). Separate analysis for each trial, however, showed that a high surgeon's caseload was beneficial for outcome in both randomized trials but not in the registration study. A subgroup analysis of 915 patients with 376 rectal and 539 colonic primaries from both randomized trials, therefore, was performed. Neither age, gender, year of operation, adjuvant chemotherapy (intraportal vs systemic vs operation alone), hospital academic status (university vs non-university), training status of the surgeon (certified surgeon vs surgeon-in-training), nor inclusion in 1 of the 2 randomized trials (SAKK 40/81 vs SAKK 40/87) was a significant predictor of outcome. However, both high surgeon's and high hospital's annual caseloads were independent, beneficial prognostic factors for OS (P = .0003, P = .044) and DFS (P = .0008, P = .020), and marginally significant factors for LR (P = .057, P = .055). CONCLUSIONS: High surgeon's and hospital's annual caseloads are strong, independent prognostic factors for extending overall and disease-free survival and reducing the rate of local recurrence in 2 randomized colorectal cancer trials.

High Ep-CAM expression is associated with poor prognosis in node-positive breast cancer.

Previous studies in small series of patients with invasive breast cancer suggested a prognostic value of Ep-CAM overexpression in primary tumor tissue. To corroborate these findings, we performed a retrospective analysis of Ep-CAM expression using a tissue microarray containing tissue specimens from a large patient set. Ep-CAM expression was evaluated by immunohistochemistry in breast cancer tissue from 1715 patients with documented raw survival data. High level Ep-CAM expression (overexpression) was found in 41.7% of tumor samples, low level expression was found in 48.0% and no expression in 10.3% of tumor samples. Ep-CAM expression predicted poor overall survival in this patient cohort (p < 0.0001). Overall survival decreased significantly with increasing Ep-CAM expression. However, in this patient sample Ep-CAM expression was not an independent prognostic marker by multivariate analysis. Subgroup analysis revealed that Ep-CAM expression was a prognostic marker in node-positive (p < 0.0001) but not in node-negative (p = 0.58) breast cancer patients. Intriguingly, Ep-CAM expression was predictive for a dismal prognosis in patients receiving adjuvant cytotoxic (p = 0.03) or hormonal therapy (p < 0.0001) but not in untreated patients (p = 0.41). In summary, this study provides strong evidence that expression of Ep-CAM is a powerful marker of poor prognosis in node-positive invasive breast carcinoma and a potential predictive marker of sensitivity to adjuvant hormonal and/or cytotoxic treatment modalities.

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. 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.

STRAP is a strong predictive marker of adjuvant chemotherapy benefit in colorectal cancer.

BACKGROUND: Molecular predictors for the effectiveness of adjuvant chemotherapy in colorectal cancer are of considerable clinical interest. To this aim, we analyzed the serine threonine receptor-associated protein (STRAP), an inhibitor of TGF-beta signaling, with regard to prognosis and prediction of adjuvant 5-FU chemotherapy benefit. METHODS: The gene copy status of STRAP was determined using quantitative real-time polymerase chain reaction in 166 colorectal tumor biopsies, which had been collected from a randomized multicenter trial of 5-fluorouracil (5-FU)/mitomycin C (MMC) adjuvant chemotherapy of the Swiss Group for Clinical Cancer Research (SAKK). RESULTS: Amplification of STRAP was found in 22.8% of the tumors. When left without adjuvant chemotherapy, patients bearing tumors with a STRAP amplification had a significantly better prognosis (hazard ratio for death: 0.26; P=.004). Interestingly, these patients, when receiving adjuvant treatment, had a worse survival (hazard ratio for death: 3.48; P=.019) than without chemotherapy, whereas patients carrying tumors with diploidy or deletion of STRAP benefited from the treatment (hazard ratio for death: 0.44; P=.052). This suggests the amplification of STRAP as a strong predictor of an unfavorable effect of 5-FU-based adjuvant chemotherapy. CONCLUSION: If confirmed, the STRAP gene copy status might provide a parameter to decide about the use of 5-FU-based adjuvant chemotherapy.

Expression of CEACAM6 in resectable colorectal cancer: a factor of independent prognostic significance.

PURPOSE: CEACAM6, CEACAM1, and human carcinoembryonic antigen (CEA) are coexpressed in normal colorectal epithelia, but show deregulated expression in colorectal cancers (CRC). Upregulation of CEACAM6 expression in hyperplastic polyps and early adenomas represents one of the earliest observable molecular events leading to colorectal tumors. The aim of our study was to evaluate the prognostic relevance of CEACAM6, CEACAM1, and CEA tissue expression in patients with CRC. PATIENTS AND METHODS: Immunohistochemical analysis was carried out on tissue microarrays from 243 paraffin-embedded biopsies from a randomized controlled clinical trial (Swiss Group for Clinical Cancer Research [SAKK] 40/81) of adjuvant fluorouracil-based chemotherapy with CEACAM-specific monoclonal antibodies. The median follow-up was 8 years. Overall survival (OS) and disease-free survival (DFS) were calculated using Kaplan-Meier estimates and hazard ratios (HRs) estimated using Cox proportional hazards models. RESULTS: Tissue expression of CEACAM6, CEACAM1, and CEA was enhanced in 55%, 58%, and 94% of patients, respectively. Multivariate Cox analysis including sex, age, tumor site, stage, differentiation grade, treatment, and nodal status as covariates showed that CEACAM6 overexpression independently predicted poor OS (HR, 1.86; P =.0100) and DFS (HR, 2.00; P =.0028), whereas CEACAM1 or CEA were not significantly related to these outcomes. The data did not provide evidence for or against the hypothesis that the CEACAM6 effect on survival differs according to treatment. CONCLUSION: Expression of the cell adhesion molecule CEACAM6 in CRC is an independent prognostic factor allowing subdivision of patients into low- and high-risk groups. Whether CEACAM6 or CEA and CEACAM1 might be useful as predictive markers of chemotherapy benefit remains unclear.

Disseminated single tumor cells as detected by real-time quantitative polymerase chain reaction represent a prognostic factor in patients undergoing surgery for colorectal cancer.

OBJECTIVE: To evaluate the clinical relevance of real-time quantitative polymerase chain reaction (qPCR) detection of CEA and CK20 transcripts, as potentially related to tumor cell dissemination, in blood and peritoneal lavage from patients undergoing surgery for colorectal cancer. SUMMARY BACKGROUND DATA: Dissemination of single colorectal cancer cells in the peritoneal cavity, as well as in tumor drainage and peripheral blood vessels, might play a role in the metastasis process, thus affecting the clinical course. However, this phenomenon needs further elucidation. METHODS: In a prospective study the authors evaluated the potential of qPCR in the detection of CEA and/or CK20 transcripts in the peritoneal lavage fluid and in the peripheral and mesenteric venous blood of 39 patients undergoing curative resection for colorectal cancer. Peritoneal lavage and peripheral blood was sampled before and after tumor resection; mesenteric venous blood was sampled from the major tumor-draining vein immediately before clamping. After RNA extraction and reverse transcription, qPCR was performed using specific cDNA primers and probes for CEA and CK20. The dichotomous results from the qPCR were used as a predictor along with other covariates in Cox proportional hazard regression models of long-term outcome (disease-free survival and overall survival). RESULTS: Of 39 patients, 11 were positive. The median follow-up at analysis was 31 months for all patients. The dichotomous qPCR covariate was significant, with P =.001 and.0035 for disease-free survival and overall survival, respectively, in the proportional hazard regression models with only qPCR. In seven patients, disseminated colorectal cancer cells were found in the peritoneal lavage fluid but not in blood specimens; five of these patients (71%) had recurrence. CONCLUSIONS: These data suggest that detection of mRNA coding for CEA and/or CK20 using qPCR has potential clinical utility as a prognostic marker and should be evaluated in larger clinical studies. Identification of patients at high risk for metastatic disease after curative resection of colorectal cancer might be improved by analyzing peritoneal lavage specimens in addition to blood samples. This is based on the observation that in more than half of qPCR-positive patients, disseminated colorectal cancer cells were detected in peritoneal lavage specimens but not in blood samples, and that 71% of them had recurrence.

DCR3 locus is a predictive marker for 5-fluorouracil-based adjuvant chemotherapy in colorectal cancer.

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.