Befrits R, Hammarberg C, Rubio C, Jaramillo E, Tribukait B
Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
Dis Colon Rectum. 1994 Apr;37(4):313-9; discussion 319-20. doi: 10.1007/BF02053590.
This study was designed to assess the presence of DNA aneuploidy and mucosal dysplasia, respectively, in 63 patients with long-standing ulcerative colitis.
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.
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.
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.
本研究旨在分别评估63例长期溃疡性结肠炎患者中DNA非整倍体和黏膜发育异常的情况。
采用流式细胞术研究结肠活检组织中的DNA含量,并与传统组织学检查结果进行比较。随后,对患者每年或每两年进行一次结肠镜检查和组织学检查。10年后进行第二次流式细胞术检查以监测DNA模式。
最初,在13/63(21%)的患者中发现了异常DNA模式(即非整倍体)。结肠黏膜扁平的有10例,息肉样的有1例,肿瘤浸润的有2例。10例黏膜扁平的非整倍体病例中有8例未显示组织学发育异常迹象。在2例同时存在非整倍体和低级别发育异常的病例中,有1例在随后的结肠切除术中发现为Dukes B期癌。另一方面,在初始检查时,2例患者发现了无非整倍体的发育异常(1例低级别,1例高级别)。10年后,13例患者接受了结肠切除术,11例死亡(7例与结肠炎无关),3例失访。在其余36例结直肠完整的存活患者中,初始检查时未发现组织学发育异常病例,但发现了6例DNA非整倍体病例。在这6例非整倍体病例中,1例后来重新分类为二倍体,1例为非整倍体腺瘤性息肉(通过息肉切除术切除)。10年后随访时,其他非整倍体病例中有3/4显示出重复的异常DNA模式,现在同时伴有组织学低级别发育异常(在扁平结肠黏膜中)。最初DNA模式正常的30例患者在10年后复查时均仍为二倍体,但其中2例现在组织学上显示有低级别发育异常。
慢性溃疡性结肠炎中的DNA非整倍体似乎是稳定的,并且可能比组织学发育异常早很多年出现。它似乎是检测溃疡性结肠炎肿瘤转化的一个额外标志物。