TP53 and carcinoma: The genetic evolutionary paradigm envisages a linear sequence of changes beginning with bi-allelic inactivation of APC, followed by oncogenic KRAS mutation and culminating in inactivation of TP53 at the transition from adenoma to carcinoma.5 While there is good evidence that KRAS mutation is associated with advanced adenoma features6 and could therefore be used as objective evidence of aggression, this approach has a number of limitations.