Aberrant crypt foci as microscopic precursors of colorectal cancer

Abstract

Since the first detection of aberrant crypt foci (ACF) in carcinogen-treated mice, there have been numerous studies focusing on these microscopically visible lesions both in rodents and in humans. ACF have been generally accepted as precancerous lesions in regard to histopathological characteristics, biochemical and immunohistochemical alterations, and genetic and epigenetic alterations. ACF show variable histological features, ranging from hyperplasia to dysplasia. ACF in human colon are more frequently located in the distal parts than in the proximal parts, which is in accordance with those in colorectal cancer (CRC). The immunohistochemical expressions of carcinoembryonic antigen (CEA), beta-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 in 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 dysplastic 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.

S‐adenosyl L‐methionine inhibits azoxymethane‐induced colonic aberrant crypt foci in F344 rats and suppresses human colon cancer Caco‐2 cell growth in 3D culture

“…Aberrant crypt foci (ACF) are putative precursors of colon cancer. 35 They are considered to be surrogate biomarkers of colon cancer, particularly for the screening of chemopreventive agents. Therefore, ACF count was used as a surrogate marker in our bioassay.…”

Azoxymethane-induced rat aberrant crypt foci: Relevance in studying chemoprevention of colon cancer

“…Detailed review of the molecular features of ACF can be found in the papers by Cheng and Lai [12] and Alrawi et al [14] , and recent advances in human ACF and their potential as biomarkers of human colorectal cancer have been elegantly discussed by Orlando et al [15] , Stevens et al [16] and Gupta et al [17] . Depending on their growth/ developmental stage, ACF are heterogeneous in their molecular make-up [12][13][14] . The growth and development of ACF on one hand could be regressed or inhibited, while on the other augmented by various compounds; both depend on the ACF dynamics as well as their heterogeneity [7] .…”

“…Secondly, in the course of their dynamics, ACF undergo several genetic changes, plausibly acquire novel phenotypes conducive to their progression, and discard those that render them normal or make them susceptible to regression [12,13] . Detailed review of the molecular features of ACF can be found in the papers by Cheng and Lai [12] and Alrawi et al [14] , and recent advances in human ACF and their potential as biomarkers of human colorectal cancer have been elegantly discussed by Orlando et al [15] , Stevens et al [16] and Gupta et al [17] . Depending on their growth/ developmental stage, ACF are heterogeneous in their molecular make-up [12][13][14] .…”

Hypothalamic beta-endorphin neurons suppress preneoplastic and neoplastic lesions development in 1,2-dimethylhydrazine induced rat colon cancer model

“…As shown in Fig, 1A and B, gross appearance of colon showing large multiple tumors in cortical neurons transplanted animals but show a small size tumor in BEP neuronal treated animals. ACF are pre-neoplastic lesions that serve as biomarkers for colon cancer (15,18). Aberrant crypts stain heavily with methylene blue and are larger than normal crypts and have characteristic elliptical shape and thickened epithelial lining (Fig.…”