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. 1997 May;150(5):1805–1813.

Identification of dysplasia in human colonic aberrant crypt foci.

I M Siu 1, T G Pretlow 1, S B Amini 1, T P Pretlow 1
PMCID: PMC1858202  PMID: 9137103

Abstract

Aberrant crypt foci (ACF) are grossly invisible putative premalignant lesions in the colon. As dysplasia is considered an important precursor of colon carcinoma, we wanted to determine the presence and severity of dysplasia in human ACF. Fifty ACF from 28 patients were embedded in paraffin, cut serially, and stained with hematoxylin and eosin. Multiple slides from each ACF were evaluated for dysplasia according to a defined set of criteria. Of 50 ACF, 3 (6%) contained focal areas with severe dysplasia, ie, carcinoma in situ, 4 (8%) contained focal areas with moderate dysplasia, and 20 (40%) contained focal areas with mild dysplasia. Twenty-three ACF (46%) contained no detectable dysplasia. In 15 of 27 ACF with dysplasia, less than 50% (eg, 4 of 28, 10 of 54, and 10 of 30 sections) of the sections cut and evaluated from each ACF demonstrated dysplasia. The presence of dysplasia in a large proportion of ACF supports the hypothesis that they may be precarcinomatous.

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Selected References

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  1. Augenlicht L. H., Richards C., Corner G., Pretlow T. P. Evidence for genomic instability in human colonic aberrant crypt foci. Oncogene. 1996 Apr 18;12(8):1767–1772. [PubMed] [Google Scholar]
  2. Beckstead J. H. Optimal antigen localization in human tissues using aldehyde-fixed plastic-embedded sections. J Histochem Cytochem. 1985 Sep;33(9):954–958. doi: 10.1177/33.9.4020104. [DOI] [PubMed] [Google Scholar]
  3. Bird R. P., McLellan E. A., Bruce W. R. Aberrant crypts, putative precancerous lesions, in the study of the role of diet in the aetiology of colon cancer. Cancer Surv. 1989;8(1):189–200. [PubMed] [Google Scholar]
  4. Bird R. P. Observation and quantification of aberrant crypts in the murine colon treated with a colon carcinogen: preliminary findings. Cancer Lett. 1987 Oct 30;37(2):147–151. doi: 10.1016/0304-3835(87)90157-1. [DOI] [PubMed] [Google Scholar]
  5. Blackstone M. O., Riddell R. H., Rogers B. H., Levin B. Dysplasia-associated lesion or mass (DALM) detected by colonoscopy in long-standing ulcerative colitis: an indication for colectomy. Gastroenterology. 1981 Feb;80(2):366–374. [PubMed] [Google Scholar]
  6. Bufill J. A. Colorectal cancer: evidence for distinct genetic categories based on proximal or distal tumor location. Ann Intern Med. 1990 Nov 15;113(10):779–788. doi: 10.7326/0003-4819-113-10-779. [DOI] [PubMed] [Google Scholar]
  7. Gerdes J., Schwab U., Lemke H., Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer. 1983 Jan 15;31(1):13–20. doi: 10.1002/ijc.2910310104. [DOI] [PubMed] [Google Scholar]
  8. Heinen C. D., Shivapurkar N., Tang Z., Groden J., Alabaster O. Microsatellite instability in aberrant crypt foci from human colons. Cancer Res. 1996 Dec 1;56(23):5339–5341. [PubMed] [Google Scholar]
  9. Jen J., Powell S. M., Papadopoulos N., Smith K. J., Hamilton S. R., Vogelstein B., Kinzler K. W. Molecular determinants of dysplasia in colorectal lesions. Cancer Res. 1994 Nov 1;54(21):5523–5526. [PubMed] [Google Scholar]
  10. Konishi F., Morson B. C. Pathology of colorectal adenomas: a colonoscopic survey. J Clin Pathol. 1982 Aug;35(8):830–841. doi: 10.1136/jcp.35.8.830. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Konstantakos A. K., Siu I. M., Pretlow T. G., Stellato T. A., Pretlow T. P. Human aberrant crypt foci with carcinoma in situ from a patient with sporadic colon cancer. Gastroenterology. 1996 Sep;111(3):772–777. doi: 10.1053/gast.1996.v111.pm8780584. [DOI] [PubMed] [Google Scholar]
  12. Longacre T. A., Fenoglio-Preiser C. M. Mixed hyperplastic adenomatous polyps/serrated adenomas. A distinct form of colorectal neoplasia. Am J Surg Pathol. 1990 Jun;14(6):524–537. doi: 10.1097/00000478-199006000-00003. [DOI] [PubMed] [Google Scholar]
  13. McLellan E. A., Bird R. P. Specificity study to evaluate induction of aberrant crypts in murine colons. Cancer Res. 1988 Nov 1;48(21):6183–6186. [PubMed] [Google Scholar]
  14. McLellan E. A., Medline A., Bird R. P. Dose response and proliferative characteristics of aberrant crypt foci: putative preneoplastic lesions in rat colon. Carcinogenesis. 1991 Nov;12(11):2093–2098. doi: 10.1093/carcin/12.11.2093. [DOI] [PubMed] [Google Scholar]
  15. McLellan E. A., Medline A., Bird R. P. Sequential analyses of the growth and morphological characteristics of aberrant crypt foci: putative preneoplastic lesions. Cancer Res. 1991 Oct 1;51(19):5270–5274. [PubMed] [Google Scholar]
  16. Otori K., Sugiyama K., Hasebe T., Fukushima S., Esumi H. Emergence of adenomatous aberrant crypt foci (ACF) from hyperplastic ACF with concomitant increase in cell proliferation. Cancer Res. 1995 Nov 1;55(21):4743–4746. [PubMed] [Google Scholar]
  17. Powell S. M., Zilz N., Beazer-Barclay Y., Bryan T. M., Hamilton S. R., Thibodeau S. N., Vogelstein B., Kinzler K. W. APC mutations occur early during colorectal tumorigenesis. Nature. 1992 Sep 17;359(6392):235–237. doi: 10.1038/359235a0. [DOI] [PubMed] [Google Scholar]
  18. Pretlow T. P., Barrow B. J., Ashton W. S., O'Riordan M. A., Pretlow T. G., Jurcisek J. A., Stellato T. A. Aberrant crypts: putative preneoplastic foci in human colonic mucosa. Cancer Res. 1991 Mar 1;51(5):1564–1567. [PubMed] [Google Scholar]
  19. Pretlow T. P., Brasitus T. A., Fulton N. C., Cheyer C., Kaplan E. L. K-ras mutations in putative preneoplastic lesions in human colon. J Natl Cancer Inst. 1993 Dec 15;85(24):2004–2007. doi: 10.1093/jnci/85.24.2004. [DOI] [PubMed] [Google Scholar]
  20. Pretlow T. P., Cheyer C., O'Riordan M. A. Aberrant crypt foci and colon tumors in F344 rats have similar increases in proliferative activity. Int J Cancer. 1994 Feb 15;56(4):599–602. doi: 10.1002/ijc.2910560422. [DOI] [PubMed] [Google Scholar]
  21. Pretlow T. P., O'Riordan M. A., Kolman M. F., Jurcisek J. A. Colonic aberrant crypts in azoxymethane-treated F344 rats have decreased hexosaminidase activity. Am J Pathol. 1990 Jan;136(1):13–16. [PMC free article] [PubMed] [Google Scholar]
  22. Pretlow T. P., O'Riordan M. A., Pretlow T. G., Stellato T. A. Aberrant crypts in human colonic mucosa: putative preneoplastic lesions. J Cell Biochem Suppl. 1992;16G:55–62. doi: 10.1002/jcb.240501111. [DOI] [PubMed] [Google Scholar]
  23. Pretlow T. P., Roukhadze E. V., O'Riordan M. A., Chan J. C., Amini S. B., Stellato T. A. Carcinoembryonic antigen in human colonic aberrant crypt foci. Gastroenterology. 1994 Dec;107(6):1719–1725. doi: 10.1016/0016-5085(94)90812-5. [DOI] [PubMed] [Google Scholar]
  24. Riddell R. H., Goldman H., Ransohoff D. F., Appelman H. D., Fenoglio C. M., Haggitt R. C., Ahren C., Correa P., Hamilton S. R., Morson B. C. Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical applications. Hum Pathol. 1983 Nov;14(11):931–968. doi: 10.1016/s0046-8177(83)80175-0. [DOI] [PubMed] [Google Scholar]
  25. Roncucci L., Medline A., Bruce W. R. Classification of aberrant crypt foci and microadenomas in human colon. Cancer Epidemiol Biomarkers Prev. 1991 Nov-Dec;1(1):57–60. [PubMed] [Google Scholar]
  26. Roncucci L., Pedroni M., Fante R., Di Gregorio C., Ponz de Leon M. Cell kinetic evaluation of human colonic aberrant crypts. (Colorectal Cancer Study Group of the University of Modena and the Health Care District 16, Modena, Italy). Cancer Res. 1993 Aug 15;53(16):3726–3729. [PubMed] [Google Scholar]
  27. Roncucci L., Stamp D., Medline A., Cullen J. B., Bruce W. R. Identification and quantification of aberrant crypt foci and microadenomas in the human colon. Hum Pathol. 1991 Mar;22(3):287–294. doi: 10.1016/0046-8177(91)90163-j. [DOI] [PubMed] [Google Scholar]
  28. Shi S. R., Imam S. A., Young L., Cote R. J., Taylor C. R. Antigen retrieval immunohistochemistry under the influence of pH using monoclonal antibodies. J Histochem Cytochem. 1995 Feb;43(2):193–201. doi: 10.1177/43.2.7822775. [DOI] [PubMed] [Google Scholar]
  29. Smith A. J., Stern H. S., Penner M., Hay K., Mitri A., Bapat B. V., Gallinger S. Somatic APC and K-ras codon 12 mutations in aberrant crypt foci from human colons. Cancer Res. 1994 Nov 1;54(21):5527–5530. [PubMed] [Google Scholar]
  30. Stopera S. A., Murphy L. C., Bird R. P. Evidence for a ras gene mutation in azoxymethane-induced colonic aberrant crypts in Sprague-Dawley rats: earliest recognizable precursor lesions of experimental colon cancer. Carcinogenesis. 1992 Nov;13(11):2081–2085. doi: 10.1093/carcin/13.11.2081. [DOI] [PubMed] [Google Scholar]
  31. Yamashita N., Minamoto T., Ochiai A., Onda M., Esumi H. Frequent and characteristic K-ras activation and absence of p53 protein accumulation in aberrant crypt foci of the colon. Gastroenterology. 1995 Feb;108(2):434–440. doi: 10.1016/0016-5085(95)90071-3. [DOI] [PubMed] [Google Scholar]

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