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


OBJECTIVE
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.


CONCLUSIONS
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.
Burum-Auensen
E
E
The Pathology Clinic, Rikshospitalet-Radiumhospitalet Medical Center, University of Oslo, Faculty of Medicine, Oslo, Norway. espen.burum-auensen@medisin.uio.no
Deangelis
P M
PM
Schjølberg
A R
AR
Røislien
Jo
J
Andersen
S N
SN
Clausen
O P F
OP
D064127:Aurora Kinases; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D003082:Colectomy; D003093:Colitis, Ulcerative / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003110:Colonic Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D064246:Mad2 Proteins; D009363:Neoplasm Proteins / Q000378:metabolism; D011003:Ploidies; D011230:Precancerous Conditions / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism
D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D064127:Aurora Kinases; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases