Fig. 4

SMAD4 expression varied by tumor site and lower SMAD4 expression in the primary tumor correlated with the patient presenting with metastasis at the time of surgery. a Immunohistochemical staining of the SINET tissue microarray revealed that low expression of SMAD4 was more frequent in both primary tumors and lymph node metastases compared to hepatic metastases for tumors with one SMAD4 copy. b Comparing SMAD4 protein expression in the primary tumor between patients with localized disease (stage I, IIA, and IIB), lymph node metastases (stage IIIB), and distant metastases (stage IV) showed that patients with low SMAD4 protein expression in the primary tumors more often presented with metastatic disease. Asterisks indicate statistically significant changes (Mann Whitney U-test): * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001