Aberrant crypt foci in patients with a positive family history of sporadic colorectal cancer

Stevens, Richard G.; Swede, Helen; Heinen, Christopher D.; Jablonski, M; Grupka, Michael; Ross, Barry; Parente, Melissa; Tirnauer, Jennifer S.; Giardina, Charles; Rajan, T. V.; Rosenberg, Daniel W.; Levine, Joel B.

doi:10.1016/j.canlet.2006.08.003

Cited by 37 publications

(33 citation statements)

References 23 publications

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“…The option to study only rectal ACF, in accordance with studies that applied a similar methodology [19][20][21][22][23][24][25][26], deserves some justification. 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.…”

Section: Discussionmentioning

confidence: 99%

“…The modulation of ACF by chemopreventive agents with proven activity in CRC is also described in animal studies [16][17][18]. With the emergence of magnification and chromoscopy, it is now possible to perform endoscopic in vivo human studies [19][20][21][22][23][24][25][26]. Although there are a number of arguments supporting the preneoplastic nature of ACF, such as an average number that increases with age [23], a higher prevalence in patients with neoplastic lesion of the colon [23], the identification of ACF with carcinoma in situ in a patient with sporadic colon cancer [27], the presence of ACF with dysplasia and APC mutations in patients with familial adenomatous polyposis [28,29], and the occurrence of microsatellite instability in ACF picked from patients with Lynch syndrome [30], the truth is that doubt still persists with regard the preneoplastic nature of ACF, which is unquestionable only in animal models of intestinal cancer.…”

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confidence: 99%

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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%

mentioning

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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“…Table 3 provides a summary of the main findings from the epidemiological studies so far reported. The total number of ACF in patients over age 50 was found to be higher in older patients than middleaged patients in the studies that presented data on age [48,49,50,56,57,59]. Of the three studies examining family history of CRC, two reported no association [56,57; based on only 3 and 4 subjects] whereas one study [59; based on 43 subjects] reported a significantly higher ACF number in patients with a family history compared to those without.…”

Section: Findings From the First-generation Studiesmentioning

confidence: 96%

“…These studies have estimated the prevalence and/or histological grade of ACF in 'normal' subjects, and subjects with colonic polyps or colon cancer [8,[48][49][50][51][52][53][54][55][56][57][58][59], although the definition of 'normal' varies widely. None of these studies has been population-based, and very few have included patients with no apparent risk factors for CRC.…”

Section: Review Of Epidemiological Studiesmentioning

confidence: 99%

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Epidemiology of colonic aberrant crypt foci: Review and analysis of existing studies

2007

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Since first described in a rodent model in 1987, aberrant crypt foci (ACF) in the colon have been shown to exhibit many of the molecular features of the more advanced colonic neoplasms including cancer. Therefore, they may be early lesions with potential for progression, and be valuable biomarkers for reduction of risk of colorectal cancer (CRC). For this review, we searched PubMed, and reference lists of recent publications, for studies which reported on associations of features of ACF in humans, such as number or size, with subject characteristics, such as age or family history of CRC. Over 150 papers have reported on ACF in humans. However, the vast majority of these publications are concerned with molecular and morphological features of biopsied lesions, and not their epidemiology. None of the epidemiological studies were of optimum design, primarily due to their absence of a well-defined subject sampling frame or method. Given their 'first-generation' nature, consistent findings were of increased ACF number with age and with synchronous advanced colonic neoplasia. One study reported a higher mean number of ACF in subjects with a family history of CRC than in those without. The strongest evidence on the ability of ACF to predict a diagnosis of CRC will be from prospective studies with baseline ACF assessment in a large sample of diseasefree persons (many thousands) who are followed carefully for many years. In the interim, because ACF are asymptomatic, well-designed cross-sectional studies are feasible and will yield valuable information on the relation of ACF to the known risk factors for CRC. This information can then be used to improve the design of prospective studies, and of clinical intervention trials that use ACF as an intermediate endpoint.

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