Histological features of advanced colorectal adenomas detected by endoscopy and fecal immunochemical test

Background and study aims: The detection of advanced adenomas within organized screening programs using either immunochemical fecal occult blood test (FIT) or endoscopy has been associated with the prevention of colorectal cancer. The histological changes and pathogenetic mechanisms that lead to the detection of such lesions by either of these screening methods have not yet been addressed.

Patients and methods: The histological specimens of 50 advanced adenomas detected by FIT were compared with those of 50 advanced adenomas detected by primary endoscopy screening that were matched for size and histology. The following variables were systematically recorded: 1) histopathological changes compatible with luminal bleeding induced by ischemia; 2) hypoxia in the adenomatous tissue, assessed through the expression of carbonic anhydrase IX; and 3) microvessel quantitative analysis, evaluated by CD31 and CD105 immunostains. All specimens were reviewed blindly by an expert gastrointestinal pathologist.

Results: Histopathological changes associated with ischemia-related luminal bleeding were significantly more frequent in FIT-positive than in endoscopy-detected advanced adenomas (78 % vs. 14 %; P < 0.001). Carbonic anhydrase IX expression was also significantly higher in FIT-detected advanced adenomas (immunohistochemical score: 12.0 vs. 4.1; P < 0.001). Conversely, no differences were found in microvessel density.

Conclusions: The detection of advanced adenomas by FIT screening appears to be related to ischemia-associated luminal bleeding, which, in turn, may be due to periods of hypoxia. The absence of such changes in endoscopy-detected advanced adenomas would suggest that the two screening methods may be complementary for the detection of advanced neoplasia within organized screening programs.

• References

• 1 Heresbach D, Manfredi S, D’halluin PN et al. Review in depth and meta-analysis of controlled trials on colorectal cancer screening by faecal occult blood test. Eur J Gastroenterol Hepatol 2006; 18: 427-433
• 2 Mandel JS, Church TR, Bond JH et al. The effect of fecal occult-blood screening on the incidence of colorectal cancer. New Engl J Med 2000; 343: 1603-1607
• 3 Guittet L, Bouvier V, Mariotte N et al. Comparison of a guaiac and an immunochemical faecal occult blood test for the detection of colonic lesions according to lesion type and location. Br J Cancer 2009; 100: 1230-1235
• 4 Zorzi M, Fedeli U, Schievano E et al. Impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test. Gut 2015; 64: 784-790
• 5 Moore RA, Derry S, McQuay HJ. Faecal blood loss with aspirin, nonsteroidal anti-inflammatory drugs and cyclo-oxygenase-2 selective inhibitors: systematic review of randomized trials using autologous chromium-labelled erythrocytes. Arthritis Res Ther 2008; 10: R7
• 6 Levi Z, Rozen P, Hazazi R et al. A quantitative immunochemical fecal occult blood test for colorectal neoplasia. Ann Intern Med 2007; 146: 244-255
• 7 Rozen P, Levi Z, Hazazi A et al. Identification of colorectal adenomas by a quantitative immunochemical faecal occult blood screening test depends on adenoma characteristics, development threshold used and number of tests performed. Aliment Pharmacol Ther 2009; 29: 906-917
• 8 Ciatto S, Martinelli F, Castiglione G et al. Association of FOBT-assessed faecal Hb content with colonic lesions detected in the Florence screening programme. Br J Cancer 2007; 96: 218-221
• 9 Foutch PG, Manne RK, Sanowski RA et al. Risk factors for blood loss from adenomatous polyps of the large bowel: a colonoscopic evaluation with histopathological correlation. J Clin Gastroenterol 1988; 10: 50-56
• 10 Uno Y, Munakata A. Endoscopic and histologic correlates of colorectal polyp bleeding. Gastrointest Endosc 1995; 41: 460-467
• 11 Hirano K, Uno Y, Munakata A et al. Factors that influence bleeding in superficial-type colorectal tumors: study of endoscopic and histologic correlates. J Gastroenterol 1996; 31: 518-524
• 12 Jain RK. Determinants of tumor blood flow: a review. Cancer Res 1988; 48: 2641-2658
• 13 Berry DP, Clarke P, Hardcastle JD et al. Randomized trial of the addition of flexible sigmoidoscopy to faecal occult blood testing for colorectal neoplasia population screening. Br J Surg 1997; 84: 1274-1276
• 14 Rasmussen M, Kronborg O, Fenger C et al. Possible advantages and drawbacks of adding flexible sigmoidoscopy to hemoccult-II in screening for colorectal cancer. A randomized study. Scand J Gastroenterol 1999; 34: 73-78
• 15 Hassan C, Giorgi RossiP, Camilloni L et al. Meta-analysis: adherence to colorectal cancer screening and the detection rate for advanced neoplasia, according to the type of screening test. Aliment Pharmacol Ther 2012; 36: 929-940
• 16 Segnan N, Senore C, Andreoni B et al. Comparing attendance and detection rate of colonoscopy with sigmoidoscopy and FIT for colorectal cancer screening. Gastroenterology 2007; 132: 2304-2312
• 17 Quirke P, Risio M, Lambert R et al. QA in pathology in colorectal cancer screening and diagnosis–European recommendations. Virchows Arch 2011; 458: 1-19
• 18 McGovern VJ, Goulston SJM. Ischaemic enterocolitis. Gut 1965; 6: 213-220
• 19 Alschibaya T, Morson BC. Ischaemic bowel disease. J Clin Pathol 1977; 30: 68-77
• 20 Rossini FP, Ferrari A, Spandre M et al. Diagnosis and management of adenomas with invasive carcinomas: an Italian experience. In: Fenoglio CM, Rossini FP, eds. Adenomas and adenomas containing invasive carcinomas of the large bowel. New York: Raven Press; 1985: 83-102
• 21 Iakovlev VV, Pintilie M, Morrison A et al. Effect of distributional heterogeneity on the analysis of tumor hypoxia based on carbonic anhydrase IX. Lab Invest 2007; 87: 1206-1217
• 22 Rasheed S, Harris AL, Tekkis PP et al. Assessment of microvessel density and carbonic anhydrase-9 (CA-9) expression in rectal cancer. Pathol Res Pract 2009; 205: 1-9
• 23 Saad RS, Liu YL, Nathan G et al. Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer. Mod Pathol 2004; 17: 197-203
• 24 Bossi P, Viale G, Lee AKC et al. Angiogenesis in colorectal tumors: microvessel quantitation in adenomas and carcinomas with clinicopathological correlations. Cancer Res 1995; 55: 5049-5053
• 25 Ransohoff DF, Lang CA. Small adenomas detected during fecal occult blood test screening for colorectal cancer. The impact of serendipity. J Am Med Assoc 1990; 264: 76-78
• 26 Dewhirst MW, Cao Y, Moeller B. Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nat Rev Cancer 2008; 8: 425-437
• 27 Halloran S, Launoy G, Zappa M. Faecal occult blood testing. In: Segnan N, Patnick J, von Karsa L, eds. European guidelines for quality assurance in colorectal cancer screening and diagnosis. Lyon: IARC Press; 2010: 103-144