Prognostic Value of Cyclin D1 and P53 Protein in Colorectal Carcinoma

There are several molecular pathways of colorectal cancer. At least four separate pathways of colorectal cancer exist: (A) adenomatous polyposis coli pathway in which B cateni-T cell factor-MYC factors are implicated (APC-B catenin-Tcf-MYC) in adenoma carcinoma sequence, (B) hereditary non-polyposis colorectal cancer pathway (HNPCC) characterized by loss of DNA mismatch repair by inherited or acquired mutation or methylation that results in microsatellite instability in tumor. Tissue specific hypermethylation of multiple genes, e.g. p16 lead to inactivation of cyclin D1-p16retinoblastoma pathway; (C) the ulcerative colitis or dysplasia-carcinoma sequence that is usually not associated with APC mutation or polyp formation. p53 loss can occur early in this pathway; (D) hypermethylation silencing of the estrogen receptor gene, which may be part of a wider pattern of gene-specific hypermethylation-common in sporadic tumors. Expression of key genes in any of these pathways may be lost by inherited or acquired mutation or by hypermethylation [38].