Adenoma-carcinoma sequence

Figure 127 is an overview of the adenoma-carcinoma model. The adenoma-carcinoma sequence of tumor development reflects an accumulation of mutations within colonic epithelium which confer a selective growth advantage to the affected cells. Key elements of this process include hyperprohferation of epithelial cehs to form a small benign neoplasm or adenoma in conjunction with cehular gene mutations. These mutations occur early and frequently in sporadic cases of both adenomas and colorectal cancer. Somatic mutations... 

Mutational inactivation of two additional important tumor suppressor genes, p53, located on chromosome 17p, and the DPC-4 (deleted in pancreatic cancer) gene, located on chromosome 18q, occur later during the adenoma-carcinoma sequence. " Normal p53 gene expression is important for Gi cell-cycle arrest to facilitate DNA repair during replication, and to induce apoptosis, an irreversible cell process resulting in cell death. Inactivation of p53 occurs in up to 75% of sporadic colorectal cancers. ... 

The major upregulation of CD44 occurs at the transition from normal mucosa to adenoma, indicating that deregulation of CD44 represents an early event in the adenoma-carcinoma sequence (Abbasi et al., 1993 Heider et al., 1993 Wielenga et al., 1993 Kim et al., 1994 P. A. Jackson et al., 1995 Got-... 

Madara et al. (1983) evaluated the structural evolution of DMH-in-duced rat intestinal neoplasms using the same criteria that were applied to evaluate human colonic adenocarcinomas. These authors showed that many DMH-induced adenocarcinomas in rats have peripheral foci of adenomatous epithelium associated with them. In addition, the frequency of this association correlates inversely with the depth of invasion. These findings are similar to those seen in humans, which have been used as evidence supporting the adenoma-carcinoma sequence. Thus, when assessed using equivalent criteria, DMH-induced intestinal adenocarcinomas appear to be similar to human colonic adenocarcinomas in their... 

The neoplastic lesions support the adenoma-carcinoma sequence as well as the novo hypothesis of cancer evolution. 

Madara, J. L., Deasy, J., Ross, D., Lahey, S., and Steele Jr., G., 1983, Evidence for an adenoma-carcinoma sequence in dimethylhydrazine-induced neoplasms of rat intestinal epithelium. Am. Assoc. Pathologists 10 230. 

The progressive transformation of adenomatous polyps to invasive adenocarcinoma has been characterized as the adenoma carcinoma sequence (Muto 1975). However, because the prevalence of undetected cancer in an asymptomatic screening population is very low at ca.1%, colon polyp size is widely accepted as a surrogate end point for outcomes assessment in colorectal cancer screening programs. Thus, the concept of the advanced adenoma has been developed which is defined as an adenomatous polyp measuring 10 mm or greater... 

Corfield, A.P., Myerscough, N., Warren, B.F., Durdey, P., Paraskeva, C., and Schauer, R. Reduction of sialic acid 0-acetylation in human colonic mucins in the adenoma-carcinoma sequence. Glycoconj. J. (1999) 16, 307-317. 

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