Aberrant crypt loci as microscopic precursors of colorectal cancer

摘要： <正> Since the first detection of aberrant crypt foci (ACF) incarcinogen-treated mice,there have been numerous studiesfocusing on these microscopically visible lesions both inrodents and in humans.ACF have been generally acceptedas precancerous lesions in regard to histopathologicalcharacteristics,biochemical and immunohistochemicalalterations,and genetic and epigenetic alterations.ACF showvariable histological features,ranging from hyperplasia todysplasia.ACF in human colon are more frequently locatedin the distal parts than in the proximal parts,which is inaccordance with those in colorectal cancer (CRC).Theimmunohistochemical expressions of carcinoembryonicantigen (CEA),β-catenin,placental cadherin (P-cadherin),epithelial cadherin (E-cadherin),inducible nitric oxidesynthase (iNOS),cyclooxygenase (COX-2),and P16~(INK4a) arefound to be altered.Genetic mutations of K-ras,APC andp53,and the epigenetic alterations of CpG island methylationof ACF have also been demonstrated.Genomic instabilitiesdue to the defect of mismatch repair (MMR) system aredetectable in ACF.Two hypotheses have been proposed.One is the "dysplasia ACF-adenoma-carcinoma sequence",the other is "heteroplastic ACF-adenoma-carcinomasequence".The malignant potential of ACF,especiallydysplastic ACF,makes it necessary to reveal the nature ofthese lesions,and to prevent CRC from the earliest possiblestage.The technique of magnifying chromoscope makes itpossible to detect "in vivd" ACF,which is beneficial to coloncancer research,identifying high-risk populations for CRC,and developing preventive procedures. ... （共8頁）