Abstract

Aim: Long term ulcerative colitis (UC) increases the risk of colorectal cancer (CRC). DNA aneuploidy is a common feature of both dysplastic- and nondysplastic 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. The goal of this study was 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).

Methods: 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 were explored.

Results: The expression of Aurora A and BUB1B were significantly associated with the progressive morphologic changes of the UCCRC (p=0.01 and p=0.005 respectively). In the progression from nondysplastic- to dysplastic mucosa, Aurora A expression decreased while BUB1B expression increased (p<0.001 for both). There was an increasing incidence of aneuploidy with progression towards cancer (p=0.04), and the expression of all spindle proteins were associated with the level of Ki67 (p<0.001 for all) but not with aneuploidy.

Conclusion: This is the first study describing the spindle proteins Aurora A, BUB1B and Mad2 in UCCRC. Due to the significant differences in Aurora A and BUB1B expression in dysplastic- compared nondysplastic mucosa, these proteins may serve as putative biological markers for the progressive morphologic changes in UC associated carcinogenesis. The close relationship to Ki67 levels reflect that spindle proteins are expressed in tissues with a high proliferative rate, but a role for these proteins in the development of aneuploidy was not found in this material.