Smad4 May Help to Identify a Subset of Colorectal Cancer Patients with Early Recurrence after Curative Therapy

Background/Aims: Loss of Smad4 function is associated with the acquisition of advanced colorectal cancer phenotypes. We investigated the role of Smad4 as a prognostic marker after curative therapy. Methodology: Four hundred and twenty nine consecutive colorectal cancers were analyzed by tissue microarray-based immunohistochemical assay. Results: Smad4 protein was expressed in 61.5% (24/39), 53.1% (77/145), 41.3% (78/189) and 34.8% (16/46) of stage I, II, III and IV cancers, respectively. Lymphovascular invasion and lymph node metastasis were strongly correlated with the loss of Smad4 expression (p<0.0001 and p=0.002, respectively). Disease-free survival did not differ between Smad4-positive and Smad4-negative cancers. In stage Ill disease, time to recurrence after curative therapy was shorter in the Smad4-negative than in the Smad4-positive cancers (20.1 +/- 15.1 vs. 34.6 +/- 34.1 months, p=0.035). Conclusions: Smad4 protein is of no value in predicting recurrence after curative therapy in colorectal cancer, but it may be helpful in identifying a subset of patients with early recurrence after curative therapy.