title: Prognostic value of reduced SMAD4 expression in patients with metastatic colorectal cancer under oxaliplatin-containing chemotherapy: a translational study of the AIO colorectal study group.
abstract: BACKGROUND
  SMAD4 is a polypeptide with tumor suppressor function being investigated as a prognostic biomarker in Union Internationale Contre le Cancer stages II and III in previous studies, but its role as a prognostic marker in stage IV colorectal cancer (CRC) is still undefined. We investigated the prognostic value of reduced SMAD4 expression in patients with metastatic (mCRC) under first-line oxaliplatin-containing combination chemotherapy.
  
  
  METHODS
  Tumor samples were obtained from patients who took part in a prospective randomized phase III chemotherapy trial of the Arbeitsgemeinschaft Internistische Onkologie of the German Cancer Society colorectal study group, comparing the use of capecitabine plus oxaliplatin with infusional 5-fluorouracil (5-FU) plus oxaliplatin as first-line therapy in mCRC. SMAD4 expression was determined by immunohistochemistry.
  
  
  RESULTS
  Tumor tissues from 230 patients were obtained. Reduced SMAD4 expression was identified in 34% of samples. Patients with reduced nuclear SMAD4 expression in tumor tissue showed a shorter progression-free survival (PFS; 7.0 months vs. 8.9 months; P = .024) and overall survival (OS; 13.9 months vs. 17.8 months; P = .044) compared with patients retaining SMAD4 expression. The effect of SMAD4 expression on PFS and OS could be demonstrated in univariate and multivariate analyses.
  
  
  CONCLUSIONS
  Our data demonstrate the importance of reduced SMAD4 expression in patients with mCRC receiving chemotherapy with oxaliplatin and 5-FU.
authors: Department of Internal Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Germany.
authors: Alexander
authors: A
authors: Baraniskin
authors: Johanna
authors: J
authors: Munding
authors: Karsten
authors: K
authors: Schulmann
authors: Dominik
authors: D
authors: Meier
authors: Rainer
authors: R
authors: Porschen
authors: Hendrik-Tobias
authors: HT
authors: Arkenau
authors: Ullrich
authors: U
authors: Graeven
authors: Wolff
authors: W
authors: Schmiegel
authors: Andrea
authors: A
authors: Tannapfel
authors: Anke
authors: A
authors: Reinacher-Schick