Spindle proteins Aurora A and BUB1B, but not Mad2, are aberrantly expressed in dysplastic mucosa of patients with longstanding ulcerative colitis

Abstract

Background: 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. Aims: 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 was explored. Results: 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. Conclusion: 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.

BubR1 as a prognostic marker for recurrence-free survival rates in epithelial ovarian cancers

“…Therefore, our results showing that BubR1 elevation is correlated with poor prognosis, cancer aggression, and RFS may reflect the proliferative capacity of tumour cells. It is very likely that the expression of BubR1 is elevated in cycling cells (Burum-Auensen et al, 2007b). Therefore, we speculate that the elevated level of BubR1 coincides with a high mitotic index.…”

“…Related to our study, an overexpression of BubR1 has been observed in several human cancers, including breast, gastric, bladder, kidney, and colorectal carcinomas (Myrie et al, 2000;Shichiri et al, 2002;Grabsch et al, 2003;Yamamoto et al, 2007;Pinto et al, 2008). In addition, it has been reported that the overall pattern of BubR1 localisation, revealed by immunostaining, differed between normal and malignant tissues in bladder, colon, pancreas, and skin cancers (Shin et al, 2003;Yamamoto et al, 2007;Burum-Auensen et al, 2007b).…”

Identification of novel compounds that enhance colon cancer cell sensitivity to inflammatory apoptotic ligands

“…This alteration may occur early in cancer development-it has been reported that Aurora kinase A and Bub1B are overexpressed in preneoplastic mucosa of ulcerative colitis patients. 64 Aberrant expression of proteins that promote mitosis may help ensure that cells do not regard, the results of our compound screen indicate that mitotic regulators may play an important role in helping cancer cells resist death ligands within the inflammatory milieu of a neoplastic lesion. Colon cancer cells have long been noted for altered expression of proteins involved in mitosis.…”

Association between Ki67 Index and Clinicopathological Features in Colorectal Cancer

“…With regard to colon tissue, Ki67 was found to be highly expressed in the proliferative basal half of the crypt [15]. Also, it has been shown that Ki67 was significantly elevated in ulcerative colitis (UC) colons compared to non-UC control samples, indicating that proliferation is enhanced in UC colonic mucosa [16]. With regard to CRC itself, it has been reported that Ki67 expression correlates with patient age, pathological tumor differentiation, and lymph node involvement [17].…”