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Clin Colorectal Cancer. 2011 Mar 1;10(1):24-9. doi: 10.3816/CCC.2011.n.003.

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.

Author information

1
Department of Internal Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Germany.

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.

PATIENTS AND 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.

CONCLUSION:

Our data demonstrate the importance of reduced SMAD4 expression in patients with mCRC receiving chemotherapy with oxaliplatin and 5-FU.

PMID:
21609932
DOI:
10.3816/CCC.2011.n.003
[Indexed for MEDLINE]

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