Burum-Auensen E, Deangelis P M, Schjølberg A R, Røislien Jo, Andersen S N, Clausen O P F
The Pathology Clinic, Rikshospitalet-Radiumhospitalet Medical Center, University of Oslo, Faculty of Medicine, Oslo, Norway.
J Clin Pathol. 2007 Dec;60(12):1403-8. doi: 10.1136/jcp.2006.044305. Epub 2007 Feb 23.
Long term ulcerative colitis (UC) increases the risk of colorectal cancer (CRC). DNA aneuploidy is a common feature of both dysplastic and non-dysplastic colonic epithelia from patients with longstanding UC, and is regarded as an early sign of possible malignant transformation. The spindle proteins Aurora A, BUB1B and Mad2 have been implicated as contributors to aneuploidy and carcinogenesis.
To investigate the role of these spindle proteins in relation to DNA aneuploidy and during the progressive morphological changes in ulcerative colitis associated colorectal cancer (UCCRC).
Tissue microarrays were made from 31 colectomy specimens from patients with longstanding UC. Expression of Aurora A, BUB1B and Mad2 was investigated by immunohistochemistry and their relation to ploidy status, mucosal morphology and Ki67 levels was explored.
Expression of Aurora A and BUB1B was significantly associated with the progressive morphological changes of UCCRC. In the progression from non-dysplastic to dysplastic mucosa, Aurora A expression decreased while BUB1B expression increased. There was an increasing incidence of aneuploidy with progression towards cancer; expression of all spindle proteins was associated with the level of Ki67 but not with aneuploidy.
Due to the significant differences in Aurora A and BUB1B expression in dysplastic compared non-dysplastic mucosa, these proteins may serve as putative biological markers for the progressive morphological changes in UC associated carcinogenesis. The close relationship to Ki67 levels reflect that spindle proteins are expressed in tissues with a high proliferative rate; a role for these proteins in the development of aneuploidy was not found.
长期溃疡性结肠炎（UC）会增加患结直肠癌（CRC）的风险。DNA非整倍体是长期患UC患者发育异常和未发育异常的结肠上皮细胞的共同特征，被视为可能发生恶性转化的早期迹象。纺锤体蛋白极光激酶A（Aurora A）、BUB1B和Mad2被认为是导致非整倍体和致癌作用的因素。
研究这些纺锤体蛋白在DNA非整倍体以及溃疡性结肠炎相关结直肠癌（UCCRC）形态学逐渐变化过程中的作用。
从31例长期患UC患者的结肠切除标本制作组织微阵列。通过免疫组织化学研究Aurora A、BUB1B和Mad2的表达，并探讨它们与倍性状态、黏膜形态和Ki67水平的关系。
Aurora A和BUB1B的表达与UCCRC的形态学逐渐变化显著相关。在从未发育异常黏膜向发育异常黏膜进展过程中，Aurora A表达降低而BUB1B表达增加。随着向癌症进展，非整倍体的发生率增加；所有纺锤体蛋白的表达均与Ki67水平相关，但与非整倍体无关。
由于发育异常黏膜与未发育异常黏膜中Aurora A和BUB1B表达存在显著差异，这些蛋白可能作为UC相关致癌过程中形态学逐渐变化的假定生物学标志物。与Ki67水平的密切关系反映出纺锤体蛋白在增殖率高的组织中表达；未发现这些蛋白在非整倍体形成过程中的作用。
