SMAD4/DPC4 Expression and Prognosis in Human Colorectal Cancer

Abstract

Background: Colorectal cancer (CRC) is one of the most common malignancies in Western countries. One major event during CRC development is loss of genetic material on chromosome 18, on which the smad4/dpc4 gene is located. SMAD4 is an important mediator of intracellular signaling in the TGF-β pathway. The functional inactivation of SMAD4 has been reported to occur in CRC. Materials and Method: The protein expression of SMAD4 was evaluated immunohistochemically in 86 formalin-fixed and paraffin-embedded CRC samples. The results were related to clinicopathological variables including survival. Results: The loss of nuclear SMAD4 protein expression was observed in 9.3% of the investigated CRCs and was correlated to poor prognosis in univariate Kaplan-Meier (p=0.034) as well as in multivariate Cox-regression (p=0.028) analyses. Conclusion: The loss of nuclear SMAD4 protein expression occurs in a subset of CRC and is associated with poor prognosis.