SMAD4 and colorectal cancer: Although experimental data suggest tumour suppressive effects of functionally active Smad4[38,39] and loss of Smad4 in colorectal cancer is associated with advanced stage disease, presence of lymph node metastasis and poor prognosis [40-43], others reported retained Smad4 expression in high-grade colorectal carcinoma and suggested loss of Smad4 is a late event in colorectal carcinogenesis [44].