Skip to main content

Advertisement

SpringerLink
Log in

DNA aneuploidy and histologic dysplasia in long-standing ulcerative colitis

A 10-year follow-up study

  • Original Contributions
  • Published:
Diseases of the Colon & Rectum

Abstract

PURPOSE: This study was designed to assess the presence of DNA aneuploidy and mucosal dysplasia, respectively, in 63 patients with long-standing ulcerative colitis. METHODS: The DNA content in colonic biopsies was investigated, using a flow cytometry method, and compared with conventional histology. Patients were subsequently followed each or every second year with colonoscopy and histology. A second flow cytometry examination to monitor the DNA pattern was performed after 10 years. RESULTS: Initially, abnormal DNA pattern (i.e.,aneuploidy) was found in 13/63 (21 percent) patients. The colonic mucosa was flat in 10, polypoid in 1, and tumor infiltrated in 2. Eight of the 10 aneuploid cases with a flat mucosa showed no signs of histologic dysplasia. In one of two cases with simultaneous aneuploidy and low-grade dysplasia, a carcinoma Dukes B was found at subsequent colectomy. On the other hand, dysplasia (one low grade and one high grade) without aneuploidy was found in two patients at the initial investigation. After 10 years, 13 had been colectomized, 11 had died (7 noncolitis related), and 3 were lost to follow-up. In the remaining 36 living patients with intact colorectum, no case of histologic dysplasia, but 6 cases of DNA aneuploidy were discovered at the initial investigation. Of the six aneuploid cases, one was later reclassified as diploid and one consisted of an aneuploid adenomatous polyp (removed by polypectomy). At follow-up 10 years later, 3/4 of the other aneuploid cases showed repeated abnormal DNA pattern, now together with histologic low-grade dysplasia (in flat colon mucosa). The 30 patients with initially normal DNA patterns were all still diploid at reexamination 10 years later, but 2 now revealed low-grade dysplasia histologically. CONCLUSIONS: DNA aneuploidy in chronic ulcerative colitis seems to be stable and it may precede histologic dysplasia by many years. It appears to be an additional marker for detecting neoplastic transformation in ulcerative colitis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Greenstein AJ, Sachar DB, Smith H,et al. Cancer in universal and left-sided ulcerative colitis: factors determining risk. Gastroenterology 1979;77:290–4.

    PubMed  CAS  Google Scholar 

  2. Edwards FC, Truelove SC. Course and prognosis of ulcerative colitis. Part IV. Carcinoma of the colon. Gut 1964;5:15–22.

    Google Scholar 

  3. De Dombal FT, Watts J, Watkinsson G, Coligher JC. Local complications of ulcerative colitis: stricture, pseudopolyposis and carcinoma of colon and rectum. BMJ 1966;1:1442–7.

    Article  PubMed  Google Scholar 

  4. Devroede GJ, Taylor WF, Sauer WG, Jackman RJ, Stickler GB. Cancer risk and life expectancy of children with ulcerative colitis. N Engl J Med 1971;285:17–21.

    Article  PubMed  CAS  Google Scholar 

  5. Lennard-Jones JE, Morson BC, Ritchie JK, Showe DC, Williams CB. Cancer risk in colitis. Assessment of the individual risk by clinical and histological criteria. Gastroenterology 1977;73:1280–9.

    PubMed  CAS  Google Scholar 

  6. Kewenter J, Ahlman H, Hulten L. Cancer in extensive ulcerative colitis. Ann Surg 1978;188:824–8.

    PubMed  CAS  Google Scholar 

  7. Bonnevie O, Binder V, Anthonisen P, Riis P. The prognosis of ulcerative colitis. Scand J Gastroenterol 1974;9:81–91.

    PubMed  CAS  Google Scholar 

  8. Gyde SN, Prior P, Allan RN,et al. Colorectal cancer in ulcerative colitis: a cohort study of primary referral centers. Gut 1988;29:206–17.

    PubMed  CAS  Google Scholar 

  9. Langholtz E, Munkholm P, Davidsen M, Binder V. Colorectal cancer risk and mortality in patients with ulcerative colitis. Gastroenterology 1992;103:1444–51.

    Google Scholar 

  10. Morson BC, Pang LS. Rectal biopsy as an aid to cancer control in ulcerative colitis. Gut 1967;8:423–34.

    PubMed  CAS  Google Scholar 

  11. Lennard Jones JE, Melville DM, Morson BC, Ritchie JK, Williams CB. Precancer and cancer in extensive ulcerative colitis: findings among 401 patients over 22 years. Gut 1990;31:800–6.

    PubMed  CAS  Google Scholar 

  12. Leidenius M, Kellokumpu Husa A, Riihelä M, Sipponen P. Dysplasia and carcinoma in longstanding ulcerative colitis: an endoscopic and histological surveillance programme. Gut 1991;32:1521–5.

    PubMed  CAS  Google Scholar 

  13. Riddel RH, Goldman H, Ransohoff DF,et al. Dysplasia in inflammatory bowel disease. Standardized classification with provisional clinical applications. Hum Pathol 1983;14:931–6.

    Google Scholar 

  14. Dixon MF, Brown LJ, Gilmour HM,et al. Observer variation in the assessment of dysplasia in ulcerative colitis. Histopathology 1988;13:385–8.

    PubMed  CAS  Google Scholar 

  15. Hammarberg C, Slezak P, Tribukait B. Early detection of malignancy in ulcerative colitis. A flow cytometry study. Cancer 1984;53:291–5.

    PubMed  CAS  Google Scholar 

  16. Löfberg R, Tribukait B, öst å, Bromström O, Reichard H. Flow cytometric DNA analysis in longstanding ulcerative colitis: a method of prediction of dysplasia and carcinoma development? Gut 1987;28:1100–6.

    PubMed  Google Scholar 

  17. Rutegård J, åhsgren L, Stenling R, Roos G. DNA content in ulcerative colitis: flow cytometric analysis in a patient series from a defined area. Dis Colon Rectum 1988;31:710–5.

    PubMed  Google Scholar 

  18. Melville DM, Jass JR, Shepherd NA,et al. Dysplasia and deoxyribonucleic acid aneploidy in the assessment of precancerous changes in chronic ulcerative colitis. Observer variations and correlations. Gastroenterology 1988;95:668–75.

    PubMed  CAS  Google Scholar 

  19. Löfberg R, Caspersson T, Tribukait B, öst å. Comparative DNA analyses in longstanding ulcerative colitis with aneuploidy. Gut 189;30:1731–6.

  20. Löfberg R, Broström O, Karlen P, Tribukait B, öst å. Colonoscopic surveillance in long-standing total ulcerative colitis—a 15 year follow up. Gastroenterology 1990;99:1021–31.

    PubMed  Google Scholar 

  21. Rubin C, Haggit R, Burmer G,et al. DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis. Gastroenterology 1992;103:1611–20.

    PubMed  CAS  Google Scholar 

  22. Löfberg R, Broström O, Karlen P, öst å. DNA aneuploidy in ulcerative colitis: Reproducibility, topographic distribution, and relation to dysplasia. Gastroenterology 1992;102:1149–54.

    PubMed  Google Scholar 

  23. Tribukait B. Flow cytometry in surgical pathology and cytology of tumors of the genito-urinary tract. Adv Clinical Cytol 1984;2:163–89.

    Google Scholar 

  24. Hammarberg C, Rubio C, Slezak P, Tribukait B. Flow cytometric DNA—analyses as a means for early detection of malignancy in patients with chronic ulcerative colitis. Gut 1984;25:905–8.

    PubMed  CAS  Google Scholar 

  25. Woolrich A, DaSilva M, Korelitz B. Surveillance in the routine management of ulcerative colitis: the predictive value of low grade dysplasia. Gastroenterology 1992;103:431–8.

    PubMed  CAS  Google Scholar 

  26. Nugent F, Haggit R, Gilpin P. Cancer surveillance in ulcerative colitis. Gastroenterology 1991;100:1241–8.

    PubMed  CAS  Google Scholar 

  27. Porschen R, Robin U, Schumacher A,et al. DNA aneuploidy in Crohn's disease and ulcerative colitis: results of a comparative flow cytometric study. Gut 1992;33:663–7.

    PubMed  CAS  Google Scholar 

  28. Löfberg R, Broström O, Karlen P, öst å, Tribukait B. Carcinoma and DNA aneuploidy in Crohn's colitis—a histological and flow cytometric study. Gut 1991;32:900–4.

    PubMed  Google Scholar 

  29. Manning A, Bulgim O, Dixon M, Axon A. Screening by colonoscopy for colonic epithelial dysplasia in inflammatory bowel disease. Gut 1987;28:1489–94.

    PubMed  CAS  Google Scholar 

  30. Tribukait B, Hammarberg C, Rubio C. Ploidy and proliferation patterns in colorectal adenocarcinomas related to Duke's classification and to histopathological differentiation: a flow cytometric DNA study. Acta Pathol Microbiol Immunol Scand 1983;91:89–95.

    CAS  Google Scholar 

  31. Löfberg R, Lindquist K, Veress B, Tribukait B. Highly malignant carcinoma in Chronic ulcerative colitis without preceding dysplasia or DNA aneuploidy: report of a case. Dis Colon Rectum 1992;35:82–6.

    PubMed  Google Scholar 

  32. Lashner B. Recommendations for colorectal cancer screening in ulcerative colitis: a review of research from a single university based surveillance programe. Gastroenterology 1992;87:168–75.

    CAS  Google Scholar 

References

  1. Dawson IM, Pryse-Davies J. The development of carcinoma of the large intestine in ulcerative colitis. Br J Surg 1959;47:113–28.

    PubMed  CAS  Google Scholar 

  2. Morson BC, Pang LS. Rectal biopsy as an aid to cancer control in ulcerative colitis. Gut 1967;8:423–34.

    PubMed  CAS  Google Scholar 

  3. Lennard-Jones JE, Morson BC, Ritchie JK, Shove DC, Williams CB. Cancer in colitis: assessment of the individual risk by clinical and histological criteria. Gastroenterology 1977;73:1280–9.

    PubMed  CAS  Google Scholar 

  4. Nugent FW, Haggitt RC, Gilpin PA. Cancer surveillance in ulcerative colitis. Gastroenterology 1991;100:1241–8.

    PubMed  CAS  Google Scholar 

  5. Choi PM, Nugent FW, Schoetz DJ Jr, Silverman ML, Haggitt RC. Colonoscopic surveillance reduces mortality from colorectal cancer in ulcerative colitis. Gastroenterology 1993;105:418–24.

    PubMed  CAS  Google Scholar 

  6. Riddell RH, Goldman H, Ransohoff DF,et al. Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical applications. Hum Pathol 1983;14:931–68.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Karolinska Hospital, 10401, Stockholm, Sweden

    R. Befrits M.D.

  2. Department of Surgery, Karolinska Hospital, Stockholm, Sweden

    C. Hammarberg M.D.

  3. Department of Pathology, Karolinska Hospital, Stockholm, Sweden

    C. Rubio M.D.

  4. Department of Diagnostic Radiology, Karolinska Hospital, Stockholm, Sweden

    E. Jaramillo M.D.

  5. Medical Radiobiology, Karolinska Institute, Stockholm, Sweden

    B. Tribukait M.D.

Authors
  1. R. Befrits M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Hammarberg M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Rubio M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Jaramillo M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B. Tribukait M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported by the King Gustav (V) Jubilee Foundation, Karolinska Institute, Stockholm, Sweden.

About this article

Cite this article

Befrits, R., Hammarberg, C., Rubio, C. et al. DNA aneuploidy and histologic dysplasia in long-standing ulcerative colitis. Dis Colon Rectum 37, 313–320 (1994). https://doi.org/10.1007/BF02053590

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02053590

Key words

Search

Navigation