TP53 and adenoma: While transformation from adenoma to carcinoma is usually caused by mutations in TP53, K-RAS and DCC 18q genes [64], progression to metastasis is normally associated with the accumulation of genetic changes in APC-KRAS-TP53 (Adenomatous Polyposis Coli–Kirsten rat sarcoma viral oncogene- the tumor suppressor p53), according to the Vogelstein model [65].