Increased expression of minichromosome maintenance protein 2 in active inflammatory bowel disease.
OBJECTIVE
Minichromosome maintenance protein 2 (Mcm2) is an accurate indicator of cell cycle entry in tissue samples, but its expression in inflammatory bowel disease (IBD) has not previously been investigated. We have used immunohistochemistry to assess the expression of Mcm2, in comparison to the existing proliferation marker Ki-67, in active IBD and IBD without inflammatory activity.


METHODS
For this experimental study, sections from colonic biopsy and resection specimens of 48 patients with IBD (5 inactive/quiescent Crohn's disease (CD), 13 active CD, 19 inactive/quiescent ulcerative colitis (UC) and 11 active UC) and 15 normal controls were immunostained with antibodies to Mcm2 and Ki-67. The percentage of immunopositive epithelial nuclei was determined by calculating a labelling index (LI) for entire glands and for gland thirds (superficial, middle and basal).


RESULTS
The Mcm2 LI was significantly increased in the superficial third of glands in active vs. inactive/quiescent UC (P < 0.0001) and active vs. inactive/quiescent CD (P = 0.001). The Mcm2 LI was significantly greater than the Ki-67 LI in active IBD, both in entire glands (P < 0.0001) and in the superficial third of glands (UC, P = 0.001; CD, P = 0.0002). Mcm2 LIs for entire glands were significantly higher in UC (all cases) compared to CD (all cases) (P = 0.032).


CONCLUSIONS
There is increased cell cycle entry, as indicated by expression of Mcm2 and to a lesser extent Ki-67, in the superficial third of colonic glands in active IBD compared to inactive/quiescent IBD. Detection of Mcm2 may contribute to improved histological assessment of small tissue biopsies and may enable the development of a direct stool-based test for detection of active IBD and potentially for assessment of disease activity.
Department of General Surgery, Addenbrooke's Hospital MRC Cancer Cell Unit, Hutchison/MRC Research Centre, Cambridge, UK.
R J
RJ
Davies
I S
IS
Scott
L S
LS
Morris
S M
SM
Rushbrook
K
K
Bird
S L
SL
Vowler
M
M
Arends
R
R
Miller
N
N
Coleman
D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D003093:Colitis, Ulcerative / Q000378:metabolism; D003106:Colon / Q000378:metabolism*; D003424:Crohn Disease / Q000378:metabolism; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000096:biosynthesis
D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen