Aberrant crypt foci: endoscopic assessment and cell kinetics characterization
Abstract
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.
Keywords
Colorectal cancer Aberrant crypt foci Cell kinetics Colonoscopy Magnification ChromoscopyNotes
Potential competing interests:
none
Financial support:
this study was supported by “FCT-Fundação para a Ciência e a Tecnologia” (POCTI/0060/2003)
References
- 1.Parkin DM, Bray F, Ferlay J et al (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108PubMedCrossRefGoogle Scholar
- 2.Rex DK, Johnson DA, Lieberman DA et al (2000) Colorectal cancer prevention 2000: screening recommendations of the American College of Gastroenterology. American College of Gastroenterology. Am J Gastroenterol 95:868–877PubMedGoogle Scholar
- 3.Vogelstein B, Fearon ER, Hamilton SR et al (1988) Genetic alterations during colorectal-tumor development. N Engl J Med 319:525–532PubMedCrossRefGoogle Scholar
- 4.Bostick RM, Fosdick L, Grandits GA et al (1997) Colorectal epithelial cell proliferative kinetics and risk factors for colon cancer in sporadic adenoma patients. Cancer Epidemiol Biomarkers Prev 6:1011–1019PubMedGoogle Scholar
- 5.Roncucci L, Scalmati A, Ponz de Leon M (1991) Pattern of cell kinetics in colorectal mucosa of patients with different types of adenomatous polyps of the large bowel. Cancer 68:873–878PubMedCrossRefGoogle Scholar
- 6.Sandler RS, Baron JA, Tosteson TD et al (2000) Rectal mucosal proliferation and risk of colorectal adenomas: results from a randomized controlled trial. Cancer Epidemiol Biomarkers Prev 9:653–656PubMedGoogle Scholar
- 7.Scalmati A, Roncucci L, Ghidini G et al (1990) Epithelial cell kinetics in the remaining colorectal mucosa after surgery for cancer of the large bowel. Cancer Res 50:7937–7941PubMedGoogle Scholar
- 8.Freitas D, Goulão MH, Camacho E et al (2002) Clinical relevance of proliferation biomarkers and p53 expression in rectal mucosa and sporadic colonic adenomas: a prospective study. Hepatogastroenterology 49:1269–1274PubMedGoogle Scholar
- 9.Anti M, Armuzzi A, Morini S et al (2001) Severe imbalance of cell proliferation and apoptosis in the left colon and in the rectosigmoid tract in subjects with a history of large adenomas. Gut 48:238–246PubMedCrossRefGoogle Scholar
- 10.Martin C, Connelly A, Keku TO et al (2002) Nonsteroidal anti-inflammatory drugs, apoptosis, and colorectal adenomas. Gastroenterology 123:1770–1777PubMedCrossRefGoogle Scholar
- 11.Bernstein C, Bernstein H, Garewal H et al (1999) A bile acid-induced apoptosis assay for colon cancer risk and associated quality control studies. Cancer Res 59:2353–2357PubMedGoogle Scholar
- 12.Bird RP (1987) Observation and quantification of aberrant crypts in the murine colon treated with a colon carcinogen: preliminary findings. Cancer Lett 37:147–151PubMedCrossRefGoogle Scholar
- 13.Boivin GP, Washington K, Yang K et al (2003) Pathology of mouse models of intestinal cancer: consensus report and recommendations. Gastroenterology 124:762–777PubMedCrossRefGoogle Scholar
- 14.Bird RP, McLellan EA, Bruce WR (1989) Aberrant crypts, putative precancerous lesions, in the study of the role of diet in the aetiology of colon cancer. Cancer Surv 8:189–200PubMedGoogle Scholar
- 15.McLellan EA, Medline A, Bird RP (1991) Dose response and proliferative characteristics of aberrant crypt foci: putative preneoplastic lesions in rat colon. Carcinogenesis 12:2093–2098PubMedCrossRefGoogle Scholar
- 16.Mereto E, Frencia L, Ghia M (1994) Effect of aspirin on incidence and growth of aberrant crypt foci induced in the rat colon by 1,2-dimethylhydrazine. Cancer Lett 76:5–9PubMedCrossRefGoogle Scholar
- 17.Shpitz B, Bomstein Y, Kariv N et al (1998) Chemopreventive effect of aspirin on growth of aberrant crypt foci in rats. Int J Colorectal Dis 13:169–172PubMedCrossRefGoogle Scholar
- 18.Wargovich MJ, Chen CD, Harris C et al (1995) Inhibition of aberrant crypt growth by non-steroidal anti-inflammatory agents and differentiation agents in the rat colon. Int J Cancer 60:515–519PubMedCrossRefGoogle Scholar
- 19.Adler DG, Gostout CJ, Sorbi D et al (2002) Endoscopic identification and quantification of aberrant crypt foci in the human colon. Gastrointest Endosc 56:657–662PubMedCrossRefGoogle Scholar
- 20.Hurlstone DP, Karajeh M, Sanders DS et al (2005) Rectal aberrant crypt foci identified using high-magnification-chromoscopic colonoscopy: biomarkers for flat and depressed neoplasia. Am J Gastroenterol 100:1283–1289PubMedCrossRefGoogle Scholar
- 21.Moxon D, Raza M, Kenney R et al (2005) Relationship of aging and tobacco use with the development of aberrant crypt foci in a predominantly African–American population. Clin Gastroenterol Hepatol 3:271–278PubMedCrossRefGoogle Scholar
- 22.Rudolph RE, Dominitz JA, Lampe JW et al (2005) Risk factors for colorectal cancer in relation to number and size of aberrant crypt foci in humans. Cancer Epidemiol Biomarkers Prev 14:605–608PubMedCrossRefGoogle Scholar
- 23.Takayama T, Katsuki S, Takahashi Y et al (1998) Aberrant crypt foci of the colon as precursors of adenoma and cancer. N Engl J Med 339:1277–1284PubMedCrossRefGoogle Scholar
- 24.Yokota T, Sugano K, Kondo H et al (1997) Detection of aberrant crypt foci by magnifying colonoscopy. Gastrointest Endosc 46:61–65 JulPubMedCrossRefGoogle Scholar
- 25.Seike K, Koda K, Oda K et al (2006) Assessment of rectal aberrant crypt foci by standard chromoscopy and its predictive value goes colonic advanced neoplasms. Am J Gastroenterol 101:1362–1369PubMedCrossRefGoogle Scholar
- 26.Stevens RG, Swede H, Heinen CD et al (2007) Aberrant crypt foci in patients with the positive family history of sporadic colorectal cancer. Cancer Lett 248:262–268PubMedCrossRefGoogle Scholar
- 27.Konstantakos AK, Siu IM, Pretlow TG et al (1996) Human aberrant crypt foci with carcinoma in situ from a patient with sporadic colon cancer. Gastroenterology 111:772–777PubMedCrossRefGoogle Scholar
- 28.Otori K, Konishi M, Sugiyama K et al (1998) Infrequent somatic mutation of the adenomatous polyposis coli gene in aberrant crypt foci of human colon tissue. Cancer 83:896–900PubMedCrossRefGoogle Scholar
- 29.Takayama T, Ohi M, Hayashi T et al (2001) Analysis of K-ras, APC, and beta-catenin in aberrant crypt foci in sporadic adenoma, cancer, and familial adenomatous polyposis. Gastroenterology 121:599–611PubMedCrossRefGoogle Scholar
- 30.Pedroni M, Sala E, Scarselli A et al (2001) Microsatellite instability and mismatch-repair protein expression in hereditary and sporadic colorectal carcinogenesis. Cancer Res 61:896–899PubMedGoogle Scholar
- 31.Winawer S, Fletcher R, Rex D et al (2003) Colorectal cancer screening and surveillance: clinical guidelines and rationale-Update based on new evidence. Gastroenterology 124:544–560PubMedCrossRefGoogle Scholar
- 32.Bagnardi V, Blangiardo M, La Vecchia C et al (2001) A meta-analysis of alcohol drinking and cancer risk. Br J Cancer 85:1700–1705PubMedCrossRefGoogle Scholar
- 33.Cho E, Smith-Warner SA, Ritz J et al (2004) Alcohol intake and colorectal cancer: a pooled analysis of 8 cohort studies. Ann Intern Med 140:603–613PubMedGoogle Scholar
- 34.Giovannucci E (2001) An updated review of the epidemiological evidence that cigarette smoking increases risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev 10:725–731PubMedGoogle Scholar
- 35.Bond JH (2000) Polyp guideline: diagnosis, treatment, and surveillance for patients with colorectal polyps. Practice Parameters Committee of the American College of Gastroenterology. Am J Gastroenterol 95:3053–3063PubMedCrossRefGoogle Scholar
- 36.Lieberman DA, Weiss DG, Bond JH et al (2000) Use of colonoscopy to screen asymptomatic adults for colorectal cancer. Veterans Affairs Cooperative Study Group 380. N Engl J Med 343:162–168PubMedCrossRefGoogle Scholar
- 37.Anderson JC, Alpern Z, Sethi G et al (2005) Prevalence and risk of colorectal neoplasia in consumers of alcohol in a screening population. Am J Gastroenterol 100:2049–2055PubMedCrossRefGoogle Scholar
- 38.Bongaerts BW, of Goeij AF, of Vogel S et al (2007) Alcohol consumption and distinct molecular pathways to colorectal cancer. Br J Nutr 97:430–434PubMedCrossRefGoogle Scholar
- 39.Gondal G, Grotmol T, Hofstad B et al (2005) Lifestyle-related risk factors and chemoprevention for colorectal neoplasia: experience from the large-scale NORCCAP screening trial. Eur J Cancer Prev 14:373–379PubMedCrossRefGoogle Scholar
- 40.Nucci MR, Robinson CR, Longo P et al (1997) Phenotypic and genotypic characteristics of aberrant crypt foci in human colorectal mucosa. Hum Pathol 28:1396–1407PubMedCrossRefGoogle Scholar
- 41.Roncucci L, Modica S, Pedroni M et al (1998) Aberrant crypt foci in patients with colorectal cancer. Br J Cancer 77:2343–2348PubMedCrossRefGoogle Scholar
- 42.Takayama T, Ohi M, Hayashi T et al (2001) Analysis of K-ras, APC, and beta-catenin in aberrant crypt foci in sporadic adenoma, cancer, and familial adenomatous polyposis. Gastroenterology 121:599–611PubMedCrossRefGoogle Scholar
- 43.Jothy S, Slesak B, Harłozińska A et al (1996) Field effect of human colon carcinoma on normal mucosa: relevance of carcinoembryonic antigen expression. Tumour Biol 17:58–64PubMedCrossRefGoogle Scholar
- 44.Braakhuis BJ, Tabor MP, Kummer JA et al (2003) A genetic explanation of Slaughter’s concept of field cancerization: evidence and clinical implications. Cancer Res 63:1727–1730PubMedGoogle Scholar
- 45.Siu IM, Robinson DR, Schwartz S et al (1999) The identification of monoclonality in human aberrant crypt foci. Cancer Res 59:63–66PubMedGoogle Scholar
- 46.Shpitz B, Bomstein Y, Mekori Y et al (1997) Proliferating cell nuclear antigen as a marker of cell kinetics in aberrant crypt foci, hyperplastic polyps, adenomas, and adenocarcinomas of the human colon. Am J Surg 174:425–430PubMedCrossRefGoogle Scholar
- 47.Nobuoka A, Takayama T, Miyanishi K et al (2004) Glutathione-S-transferase P1-1 protects aberrant crypt foci from apoptosis induced by deoxycholic acid. Gastroenterology 127:428–443PubMedCrossRefGoogle Scholar
- 48.Shpitz B, Bomstein Y, Mekori Y et al (1997) Proliferating cell nuclear antigen as a marker of cell kinetics in aberrant crypt foci, hyperplastic polyps, adenomas, and adenocarcinomas of the human colon. Am J Surg 174:425–430PubMedCrossRefGoogle Scholar
- 49.Aotake T, Lu CD, Chiba Y et al (1999) Changes of angiogenesis and tumor cell apoptosis during colorectal carcinogenesis. Clin Cancer Res 5:135–142PubMedGoogle Scholar
- 50.Tsujitani S, Shirai H, Tatebe S et al (1996) Apoptotic cell death and its relationship to carcinogenesis in colorectal carcinoma. Cancer 77:1711–1716PubMedGoogle Scholar
- 51.Hao X, Du M, Bishop AE et al (1998) Imbalance between proliferation and apoptosis in the development of colorectal carcinoma. Virchows Arch 433:523–527PubMedCrossRefGoogle Scholar
- 52.Koornstra JJ, de Jong S, Hollema H et al (2003) Changes in apoptosis during the development of colorectal cancer: a systematic review of the literature. Crit Rev Oncol Hematol 45:37–53PubMedCrossRefGoogle Scholar