Immunohistochemical analyses of the expression of the encoded proteins (the SMAD4 protein and the p16 INK4A and p14 ARF proteins encoded by the CDKN2A locus) report loss of SMAD4 protein expression in approximately 55% of PDAC samples [25,26,27,28,29,30,31] and loss of p16/INK4A and p14/ARF in a slightly higher fraction of cancers. This evidence concerns the gene SMAD4 and cancer.