Aberrant crypt foci as microscopic precursors of colorectal cancer
摘要
Since the first detection of aberrant crypt foci (ACF) carcinogen-treated mice, there have been numerous studies focusing on these microscopically visible lesions both rodents and humans. ACF have been generally accepted as precancerous lesions regard to histopathological characteristics, biochemical and immunohistochemical alterations, and genetic and epigenetic alterations. ACF show variable histological features, ranging from hyperplasia to dysplasia. ACF human colon are more frequently located the distal parts than the proximal parts, which is accordance with those colorectal cancer (CRC). The immunohistochemical expressions of carcinoembryonic antigen (CEA), β-catenin, placental cadherin (P-cadherin),epithelial cadherin (E-cadherin), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and P16INK4a are found to be altered. Genetic mutations of K-ras, APC and p53, and the epigenetic alterations of CpG island methylation of ACF have also been demonstrated. Genomic instabilities due to the defect of mismatch repair (MMR) system are detectable ACF Two hypotheses have been proposed.One is the dysplasia ACF-adenoma-carcinoma sequence,the other is heteroplastic ACF-adenoma-carcinoma sequence. The malignant potential of ACF, especially dyspiastic ACF, makes it necessary to reveal the nature of these lesions, and to prevent CRC from the earliest possible stage. The technique of magnifying chromoscope makes it possible to detect in vivo' ACF, which is beneficial to colon cancer research, identifying high-risk populations for CRC,and developing preventive procedures.