AffiliationDepartment of Surgery, Christie Hospital NHS Trust, Manchester, UK, Department of Histopathology, Trafford General Hospital, Manchester, UK, Epistem Ltd, Manchester, UK.
MetadataShow full item record
AbstractColorectal cancer develops through a multistage process recognizable at a histopathological level by progression from normal mucosa to invasive carcinoma (the adenoma-carcinoma sequence). For many years, it has been hypothesized that increased cell proliferation in the colonic crypt represents the earliest recognizable stage in this sequence. This perspective is now changing. While several human studies have reported increased crypt cell proliferation in samples from at-risk patients, there are many inconsistencies and paradoxes in their conclusions. In addition, it is appreciated that the process of apoptosis (programmed cell death) is vital for normal crypt homeostasis and its impairment may be an early event in the neoplastic process. It is now believed that aberrant crypt foci (ACFs) represent the earliest step in colorectal carcinogenesis. Two ACF types are identifiable: hypercellular and dysplastic. Increased proliferative activity may be seen in both, but the dysplastic entity is most relevant to carcinogenesis. Animal and human studies support the notion that ACFs grow by crypt fission leading to the formation of microadenomas. Adenomas are monoclonal expansions of an altered cell, but very early lesions may be polyclonal. There are outward and inward theories of polypoid growth, and evidence to support both mechanisms. The ACF assay has become a useful tool to detect carcinogens in animal studies but has been less frequently used in human studies. For future cancer chemopreventive and risk assessment studies in humans, the identification and quantification of ACFs should be considered a more effective intermediate marker of risk than the determination of crypt cell proliferation alone.
CitationEarly cellular events in colorectal carcinogenesis. 2002, 4 (2):76-89 Colorectal Dis
- Proliferating cell nuclear antigen as a marker of cell kinetics in aberrant crypt foci, hyperplastic polyps, adenomas, and adenocarcinomas of the human colon.
- Authors: Shpitz B, Bomstein Y, Mekori Y, Cohen R, Kaufman Z, Grankin M, Bernheim J
- Issue date: 1997 Oct
- Aberrant crypt foci in colorectal carcinogenesis. Cell and crypt dynamics.
- Authors: Roncucci L, Pedroni M, Vaccina F, Benatti P, Marzona L, De Pol A
- Issue date: 2000 Feb
- Aberrant crypt foci in colon cancer epidemiology.
- Authors: Khare S, Chaudhary K, Bissonnette M, Carroll R
- Issue date: 2009
- Rectal aberrant crypt foci identified using high-magnification-chromoscopic colonoscopy: biomarkers for flat and depressed neoplasia.
- Authors: Hurlstone DP, Karajeh M, Sanders DS, Drew SK, Cross SS
- Issue date: 2005 Jun
- Biology and diagnosis of aberrant crypt foci.
- Authors: Lopez-Ceron M, Pellise M
- Issue date: 2012 Apr