Aberrant crypt foci in patients with colorectal cancer

Roncucci, Luca; Modica, Salvatore; Pedroni, Monica; Tamassia, Maria Grazia; Ghidoni, M; Losi, Lorena; Fante, Rossella; Gregorio, Carmela Di; Manenti, Antonio; Gafà, Lorenzo; Leòn, Maurizio Ponz de

doi:10.1038/bjc.1998.389

Cited by 51 publications

(55 citation statements)

References 21 publications

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“…This decision was founded on investigations in surgical specimens [40,41] and endoscopic studies [23,42] that show that ACF are more frequently detected in the left colon and in the rectum. We also thought that characterizing the ACF with magnification and chromoscopy in the whole colon in a large number of patients would unacceptably prolong the examination time in some cases.…”

Section: Discussionmentioning

confidence: 99%

Aberrant crypt foci: endoscopic assessment and cell kinetics characterization

Figueiredo

Donato

Urbano

et al. 2008

Int J Colorectal Dis

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Background and aims Aberrant crypt foci (ACF) are preneoplastic lesions in animal models of colorectal cancer. The aim of the study is to investigate if ACF are involved in human colorectal carcinogenic process and if they can be helpful in predicting the presence of a colorectal neoplasia. Methods The study included, between 2003 and 2005, 182 patients, 62 with adenoma, 55 with colorectal carcinoma, 53 without colorectal lesions, and 12 with nonneoplastic mucosal polyps. The number of rectal ACF was determined by colonoscopy. Proliferation and apoptosis indexes were evaluated by immunohistochemistry in rectal ACF, in normal rectal mucosa, and in carcinomatous tissue. Results The mean number of rectal ACF in patients with rectal neoplasia was 12.64, significantly higher than in patients with neoplastic lesions elsewhere in the colon (p= 0.01). The apoptosis index in ACF of patients with colorectal carcinoma or adenoma aged 50 years or older was significantly lower than in younger patients (1.3% vs 2.7%, p=0.01) and, in patients with carcinoma, lower than in normal mucosa (1.1% vs 2.1%, p=0.002). The proliferation index was significantly higher in ACF of patients with colorectal neoplasia aged less than 50 years than in normal mucosa (10.9% vs 7.7%, p=0.02). The apoptosis index in ACF foci of patients with carcinoma (1.1%) was significantly lower than in patients without lesions (2.2%) and than in normal mucosa (2%). The mean number of ACF is significantly higher in patients with polyps larger than 1 cm (11.28 vs 6.27, p=0.02). Conclusion Aberrant crypt foci probably precede the appearance of neoplasia and may be helpful in predicting the presence of a colorectal neoplastic lesion.

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Section: Discussionmentioning

confidence: 99%

Aberrant crypt foci: endoscopic assessment and cell kinetics characterization

Figueiredo

Donato

Urbano

et al. 2008

Int J Colorectal Dis

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“…88 Mucinous carcinomas decrease in frequency by approximately 2.5-fold from the proximal to distal colon. 89,90 This is in line with the more frequent expression of mucin-associated M1 antigen in proximal (55%) compared to distal (13%) tumours.…”

Section: Morphologic and Molecular Differences Between Right And Leftmentioning

confidence: 99%

Are there two sides to colorectal cancer?

Iacopetta

2002

Intl Journal of Cancer

684

558

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Colorectal carcinomas (CRC) that arise proximal (right) or distal (left) to the splenic flexure exhibit differences in incidence according to geographic region, age and gender. Together with observations that tumours in the hereditary cancer syndromes HNPCC and FAP occur predominantly in the right and left colon, respectively, the existence of 2 categories of CRC based on site of origin in the large bowel was proposed more than a decade ago. Differences between normal right and left colonic segments that could favour progression through different tumourigenic pathways are summarized in this review. Accumulating evidence suggests that the risk of CRC conferred by various environmental and genetic factors is different for proximal and distal tumours. Right-and left-sided tumours also exhibit different sensitivities to fluorouracil-based chemotherapy. Such differences are probably related to the molecular characteristics of the tumours, with the microsatellite instability and CpG island methylator phenotypes being associated with right-sided tumours and chromosomal instability with left-sided tumours. Future molecular-based classification systems for CRC that rely upon distinctive gene expression patterns may allow a clearer discrimination of subgroups than that provided by tumour site alone. Until then however, the existence of 2 broadly different groups of cancer defined by site of origin in the colon should be considered in the design of future epidemiologic studies as well as in the design of new clinical trials aimed at testing novel adjuvant therapies.

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“…(26,(60)(61)(62)(63)(64) The possibility that heteroplastic ACF are precursors of a subset of CRC is supported by several lines of evidence: (1) heteroplastic ACF are clonal; (65) (2) genetic alterations that are common in CRC, such as K-ras mutation, (26,60,61,63,64) chromosome 1p loss, (59) and CpG island methylation, (59) (66)(67)(68) and (4) ACF with mixed heteroplastic and dysplastic components have been described. (69) These findings have suggested the presence of a heteroplastic ACF-adenoma-carcinoma sequence in which K-ras mutation precedes APC mutation.…”

Section: Heteroplastic (Non-dysplastic) Acfmentioning

confidence: 99%

Genetic and epigenetic changes in aberrant crypt foci and serrated polyps

Suehiro¹,

Hinoda

2008

Cancer Science

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Aberrant crypt foci (ACF) in colorectal mucosa are the earliest known morphological precursors to colorectal cancer and can be subclassified as dysplastic, heteroplastic (non-dysplastic), and mixed types. Serrated adenoma (SA) is a polyp with serrated architecture and dysplasia, and can be subclassified as traditional SA or sessile SA. Sessile SA is thought to be preneoplastic and differs from most lesions in the traditional SA category because of their flat morphology and general lack of cytological dysplasia. Serrated polyps include hyperplastic polyps (HP), SA, and admixed hyperplastic-adenomatous polyps and are considered a morphological continuum encompassing heteroplastic ACF, HP, admixed hyperplastic-adenomatous polyps, and SA. Recent studies have uncovered other developmental pathways including a heteroplastic ACF-HP/SA-carcinoma sequence and a heteroplastic ACF-adenoma-carcinoma sequence. Heteroplastic ACF histopathologically resemble HP and SA. Sporadic HP are usually present in the left colon, are small, and are considered benign. However, adenocarcinoma arising in the setting of colorectal HP or SA, especially in patients with hyperplastic polyposis, has been described. The relationship between heteroplastic ACF, HP, and colorectal cancer is less certain than that of dysplastic ACF. Here, we discuss the current understanding of genetic and epigenetic alterations in the development of colorectal cancer. Our goal is to provide a conceptual framework for understanding the heteroplastic ACF-HP/SA-carcinoma sequence. (1) Most colorectal cancers (CRC) develop from adenomatous polyps (tubular adenoma) and show morphological and genetic progression through an adenomacarcinoma sequence, even in hereditary colorectal cancer syndromes. (2)(3)(4) Sporadic HP are usually present in the left colon, are small, and are generally regarded as harmless lesions with no potential for malignancy.(5,6) However, adenocarcinoma arising in the setting of colorectal HP or serrated adenomas (SA), especially in patients with hyperplastic polyposis (HPP), which is characterized by the presence of numerous HP or large HP, have been described.(7-11) Indeed, patients with HPP have an increased risk of CRC.(11-18) Serrated polyps (SP) include HP, SA, and admixed hyperplastic-adenomatous polyps (AHAP), (19,20) and are considered a morphological continuum encompassing non-dysplastic (heteroplastic) aberrant crypt foci (ACF), HP, AHAP, and SA. (21) SA are composed of dysplastic epithelium but with the sawtooth configuration that is typical of HP. (20) SA are subclassified as traditional SA and sessile SA. (22,23) Sessile SA is thought to be preneoplastic and differs from most lesions in the traditional SA category because of its flat morphology and general lack of cytological dysplasia. (22,23) The incidence of SA is reported to be 0.8-4.9% of colorectal tumors. (24,25) In addition, the incidence of carcinoma in SA is reported to be 1.5-19.2%, which is equal to or lower than the incidence in tubular adenoma.Recent studies have proposed ...

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Aberrant crypt foci in patients with colorectal cancer

Cited by 51 publications

References 21 publications

Aberrant crypt foci: endoscopic assessment and cell kinetics characterization

Aberrant crypt foci: endoscopic assessment and cell kinetics characterization

Are there two sides to colorectal cancer?

Genetic and epigenetic changes in aberrant crypt foci and serrated polyps

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