AbstractColon cancer evolves through epithelial cellderegulation and - PDF document

Abstract.Colon cancer evolves through epithelial cellderegulation and inappropriate proliferation. Thesehistopathological characteristics are exemplified in thebiochemical, immunohistochemical, genetic and epigeneticelements detected within colonic mucosa. Early detection isparamount for the prevention of colon cancer deaths. Aberrantcrypt foci (ACF) are thought to be the earliest identifiableneoplastic lesions in the colon carcinogenetic model. Theprogression of ACF to polyp and, subsequently, to cancerparallels the accumulation of several biochemical alterationsand mutations whereby a small fraction of ACF evolve to colon 107 ReviewAberrant Crypt FociSADIR J. ALRAWI1, MICHAEL SCHIFF2 CRCs developed from flat orwere described as appearing "reddish", less than 1 cm inwith a high

proportion of over 40% demonstrating morealternate route in CRC evolution (17-25).compared to polypoid CRC, despite the latters smaller size.reporting nodal metastasis in flat CRCs of less than 10mmbecause of their flat shape and size, can often be difficult todetect endoscopically but with the aid of HMCC, these andgenetic abnormalities in oncogenes, tumor suppressor genesplace throughout ACF evolution (10-12,32-35).cells replacing the crypt approximately every five days. Thethe formulation of ACF (36-41). unknown whether this is a field or lesion-effect phenomenon,ACF were first described and induced in aafter treatment with azoxy-methane (AOM) (4,46). Usingof colon cancer (4, 47).numerous complexes numbering in the tens to hundreds ofnormal crypt. Thus, multiple aberrant cr

ypts would form aNewmagnifi-staining and pattern of crypt lumens or "pit pattern" readilyidentifies ACF. Likewise the "pit pattern" of other lesions,employed Crystal Violet 0.05%, which has been associatedpattern in certain circumstances.An initial wash with the 109 implementation, HMCC identification of ACF is comparablefrom 5%-54% (5, 50, 68-72,77,87). The histologicaldysplastic may occur (50, 70, 80, 81). A single ACF may(6,70,78) and these remote from lesionsupporting their role as precancerous lesions (6,50,51,72,82,88-90). 2. Anatomic Location of ACF. tend to have more crypts per ACF cryptmultiplicity(48,49,59,69,71). the presence of CRC, there are other reports showing their(48, 54, 64,71,91). Takayama found that 10% of normalsubjects under the age of 40 had ACF,but that

thebecame apparent with 75% of patients under 40 having anprevalence of ACF was 100% in all age groups (59). CRC increased the relative risk ratio for dysplastic ACF byThe size of the ACF depends on crypt multiplicity, whichGardners syndrome demonstrate increased ACF size andhereditary disease predisposes patients to higher numbersassociated ACF (48, 49). This difference suggests at least twoACF form without non-dysplastic, sporadic ACF and in 63% of dysplastic,adenomas demonstrated somatic developed dysplastic ACF and neoplasia (62, 92, 93).progress while sporadic ACF are usually hyperplastic andcentral to the neoplastic transformation (43,56-58). 111 ulcerative colitis (114,115).methylation was found in 53% of sporadic ACF at 5 major93% and 87% of ACF, respectively. These loc

i are knownin ACF compared to CRC from the same patients supportfrequencies of loci methylation in several series. Althoughhypothesis that ACF are precursors to CRC (94,130,131).similar to genetic alterations (38,92,132,133).genesis is a multi-step process with frequentgeneticmutations are involved in the relatively early stages. Thesefrom trace to 95% mutation rates among variouspopulations. Most ACF are hyperplastic and positive formutations. (5,83, 100, 134-139)in both ACF and in the consequent colonic tumors in mostThese observations suggest that ACF arise as a result of 113 Table III.Gene alterations in colon cancer, adenoma and ACF. LesionMutation frequency % APCB-CateninK-rasDCCP53Adenocarcinoma40-80%15%40-60%40-70%50-80%Adenoma40-65%0%0-40%0%0% ACF0%10-95%0%0% 1Greenlee

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