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      Rectal aberrant crypt foci (ACF) as a predictor of benign and malignant neoplastic lesions in the large intestine

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          Abstract

          Background

          The importance of ACF is not fully explained, however, their number may be a good predictor of synchronous and metachronic adenoma or other polyps whose removal reduces the risk of CRC. Due to the epidemiological and genetic association of ACF with pre-cancer lesions, they may be a potential CRC biomarker. The aim of our study was to show that the number and type of rectal ACF may be a good predictive factor for the presence of polyps located proximally from the splenic flexure and that the type and number of ACF can correlate with the number and specific types of polyps in the large intestine.

          Methods

          The study included 131 patients who underwent colonoscopy combined with rectal mucosa staining with 0.25% methylene blue. The number of rectal ACF was determined and bioptats were sampled for histopathological examination to assess the type of ACF. Endoscopic ACF assessment criteria given by L. Roncucci were used. The obtained material was subjected to statistical analysis using probability distribution, U-test, t-student test, and chi 2 as well as the Statistica 7.1 software package.

          Results

          The study population was divided into three subgroups according to the number of ACF observed, i.e. ACF < 5, 5–10 and > 10. ACF < 5 were found in 35 patients (29.41%), 5–10 ACF in 70 (58.82%) and ACF > 10 in 14 individuals (11.76%).

          The study revealed the presence of normal ACF ( p = 0.49), hyperplastic ACF ( p = 0.34), dysplastic ACF ( p = 0.11), and mixed ACF ( p = 0.06). A single type of ACF was most commonly observed ( n = 88, p = 0.74). In the researched group a larger number of ACF is concurrent with adenomas and hyperplastic polyps. The number of ACF clearly correlates with the dysplasia advancement in the adenoma and the number of polyps found.

          Conclusions

          Rectal ACF are a useful marker for the presence of cancerous lesions in the proximal and distal sections of the large intestine.

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          Most cited references28

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          Aberrant crypt foci of the colon as precursors of adenoma and cancer.

          Aberrant crypt foci of the colon are possible precursors of adenoma and cancer, but these lesions have been studied mainly in surgical specimens from patients who already had colon cancer. Using magnifying endoscopy, we studied the prevalence, number, size, and dysplastic features of aberrant crypt foci and their distribution according to age in 171 normal subjects, 131 patients with adenoma, and 48 patients with colorectal cancer. We also prospectively examined the prevalence of aberrant crypt foci in 11 subjects (4 normal subjects, 6 with adenoma, and 1 with cancer) before and after the administration of 100 mg of sulindac three times a day for 8 to 12 months and compared the results with those in 9 untreated subjects (4 normal subjects and 5 with adenoma). All 20 subjects had aberrant crypt foci at base line. We identified 3155 aberrant crypt foci, 161 of which were dysplastic; the prevalence and number increased with age. There were significant (P<0.001) correlations between the number of aberrant crypt foci, the presence of dysplastic foci, the size of the foci, and the number of adenomas. After sulindac therapy, the number of foci decreased, disappearing in 7 of 11 subjects. In the untreated control group, the number of foci was unchanged in eight subjects and slightly increased in one (P<0.001 for the difference between the groups). Aberrant crypt foci, particularly those that are large and have dysplastic features, may be precursors of adenoma and cancer.
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            APC mutations and other genetic and epigenetic changes in colon cancer.

            Relationships between adenomatous polyposis coli (APC) mutations, BRAF V600E mutations, and the CpG island methylator phenotype (CIMP) in colon cancer have not been explored. In addition, controversies exist about the proportion of tumors with APC mutations in the mutation cluster region (MCR); how commonly APC, Ki-ras, and p53 mutations occur in the same tumor; and whether APC mutations occur in sporadic microsatellite-unstable tumors. The APC gene was therefore sequenced in 90 colonic adenocarcinomas previously evaluated for CIMP, microsatellite instability, BRAF, Ki-ras, and p53. APC mutations were inversely related to BRAF mutations (P = 0.0003) and CIMP (P = 0.02) and directly related to p53 and Ki-ras mutations (P = 0.04). Slightly more than half of APC mutations occurred outside of the MCR, and frameshift mutations were more likely than nonsense mutations to occur in the MCR (21 of 28 versus 12 of 40, P = 0.0003). APC mutations were found in sporadic microsatellite-unstable tumors and were more likely to be frameshifts in short nucleotide repeats (P = 0.007). The occurrence of APC, Ki-ras, and p53 mutations together in the same tumor was uncommon (11.1%). In conclusion, an analysis restricted to the MCR will miss more than half of APC mutations as well as mischaracterize their mutational spectrum. The conventional wisdom that most colon cancers contain APC, Ki-ras, and p53 mutations is incorrect. Microsatellite instability may precede acquisition of APC mutations in sporadic microsatellite-unstable tumors. The relationships of APC mutations to other genetic and epigenetic alterations add to the already impressive genetic heterogeneity of colon cancer.
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              Identification and quantification of aberrant crypt foci and microadenomas in the human colon.

              The objective of the present study was to determine whether aberrant crypt foci (ACF) similar to those observed in the colons of experimental animals exposed to colon carcinogens could be identified and quantified in the human colon. Twenty-seven colon resections from patients affected by familial adenomatous polyposis (FAP, five cases), colorectal cancer (CRC, 12 cases), and benign diseases of the large bowel (BD, 10 cases) were collected from a pathology repository or immediately after operation. Ten or more 1-cm2 formalin-fixed, methylene-blue--stained samples of colonic mucosa from each colon were scored under light microscopy for ACF. The number of ACF per cm2 and the number of crypts per ACF for each colon were calculated. The average number of ACF per cm2 in the FAP group (20 +/- 19, mean +/- SD) was significantly higher (P less than 0.01) than those of the CRC (0.37 +/- 0.41) and BD (0.18 +/- 0.35) groups. At least one ACF was found in every colon resection from CRC patients and in six out of 10 colon resections from the BD group. The average number of crypts per ACF ranged from five to 35 with absolute values from 1 to over 100. Fifty-five histologic specimens, 43 with ACF of various size and 12 without, were prepared by sectioning the colon parallel to the mucosal surface. There was a close correlation between the number of crypts per ACF in each specimen as scored by methylene-blue and histologic examination. Twenty-six aberrant crypt foci displayed dysplasia as evident by histologic analysis. In these instances we feel the term microadenoma is appropriate and, using this unique approach of examining the human colon, they can be easily identified and quantified. These lesions may well be precursors for adenomatous polyps and colorectal cancer.
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                Author and article information

                Contributors
                forel@neostrada.pl
                m.orlowski@przychodniachelm.pl
                lukasz.klepacki@uwm.edu.pl
                kzinek@yahoo.com
                wkurpiewski@interia.pl
                nurdok@o2.pl
                wieslaw.pesta@vp.pl
                ewa.zielinski.bydgoszcz@wp.pl
                nurdok@tlen.pl
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                19 February 2020
                19 February 2020
                2020
                : 20
                : 133
                Affiliations
                [1 ]Department of Oncologic and General Surgery, University Hospital in Olsztyn, Olsztyn, Poland
                [2 ]Department of Laboratory Medicine, University Hospital in Olsztyn, Olsztyn, Poland
                [3 ]Centre for Diagnosis and Treatment of Gastrointestinal Diseases, Gdańsk, Poland
                [4 ]Department of Anatomy, University Hospital in Olsztyn, Olsztyn, Poland
                [5 ]Oncological and General Surgery Clinic, University Hospital in Olsztyn, Olsztyn, Poland
                [6 ]ISNI 0000 0001 1033 7158, GRID grid.411484.c, 52nd Department of General, Gastroenterologic and Gastrointestinal Oncologic Surgery, , Medical University of Lublin, University Hospital No.1, ; Lublin, Poland
                [7 ]Department of Oncologic and General Surgery, University Hospital in Olsztyn, Olsztyn, Poland
                [8 ]ISNI 0000 0001 2370 4076, GRID grid.8585.0, WSB University of Gdańsk, ; Gdańsk, Poland
                [9 ]Department of Oncologic and General Surgery, University Hospital in Olsztyn, Olsztyn, Poland
                [10 ]ISNI 0000 0001 0943 6490, GRID grid.5374.5, Department of Emergency Medicine and Disaster Collegium Medicum in Bydgoszcz, , Nicolaus Copernicus University in Toruń, ; Toruń, Poland
                [11 ]ISNI 0000 0001 2223 4375, GRID grid.462680.e, Department of Underwater Works Technology, , Polish Naval Academy, ; Gdynia, Poland
                [12 ]ISNI 0000 0004 0620 0839, GRID grid.415641.3, Department of Maritime & Hyperbaric Medicine Department, , Military Institute of Medicine Gdynia, ; Warsaw, Poland
                Author information
                http://orcid.org/0000-0002-0013-6448
                Article
                6590
                10.1186/s12885-020-6590-4
                7029492
                32075595
                b9ea26e0-ce55-41ee-b9fc-9055ce7b2822
                © The Author(s). 2020

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 23 August 2018
                : 30 January 2020
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Oncology & Radiotherapy
                large intestine,benign and malignant neoplastic lesions,rectal acf
                Oncology & Radiotherapy
                large intestine, benign and malignant neoplastic lesions, rectal acf

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