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DNA aneuploidy and histologic dysplasia in long-standing ulcerative colitis. A 10-year follow-up study
R Befrits1, C Hammarberg, C Rubio
1Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
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 re-examination 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.