TY - JOUR
TI - Minichromosome maintenance proteins 2 and 5 expression in
muscle-invasive urothelial cancer: a multivariate survival study
including proliferation markers and cell cycle regulators
AU - Korkolopoulou, P
AU - Givalos, N
AU - Saetta, A
AU - Goudopoulou, A and
AU - Gakiopoulou, H
AU - Thymara, I
AU - Thomas-Tsagli, E
AU - Patsouris, E
JO - HUMAN PATHOLOGY
PY - 2005
VL - 36
TODO - 8
SP - 899-907
PB - W B SAUNDERS CO-ELSEVIER INC
SN - 0046-8177
TODO - 10.1016/j.humpath.2005.06.008
TODO - minichromosome maintenance proteins; muscle-invasive urothelial cancer;
cell cycle regulators
TODO - Evaluation of cell cycle regulators has gained special interest in the
effort to increase the amount of prognostic information in malignant
tumors. Minichromosome maintenance proteins (MCMs) drive the fort-nation
of prereplicative complexes, which is the first key event during G1
phase. Therefore, altered MCM expression may be a hallmark of cell cycle
deregulation, which is supposed to be the most essential mechanism in
the development and progression of bladder cancer. Our aim was to
investigate the value of MCMs as proliferation markers and prognostic
indicators in detrusor muscle-invasive urothelial bladder carcinomas. We
analyzed immunohistochemically the expression of MCM-2 and MCM-5 in 65
patients with detrusor muscle invasive urothelial bladder carcinomas in
relation with clinicopathologic parameters, patients’ overall and
disease-free survival, and the expression of the conventional
proliferation index Ki-67 and other cell cycle modulators (p53, pRb,
p21(WAF1) and p27(Kip1)). The levels of MCM-2 and MCM-5 were
significantly higher in high-grade (P <.0001), advanced-stage (P =.001),
and nonpapillary tumors (P <.0001). The expression of MCM-2 and MCM-5
significantly associated with the conventional proliferation index Ki-67
(P =.0001 for each protein). The expression of MCM-2 or MCM-5 positively
correlated with p53 labeling index (P =.014 and P =.009, respectively).
Also, median p21(WAF1) labeling index was higher in MCM-5 high
expressors (P =.028). Finally, both MCM-2 and MCM-5 associated
significantly with adverse patients’ outcome in both univariate (P
=.0072 and P =.0074, respectively) and multivariate (P =.0001) analysis.
In conclusion, MCM-2 and MCM-5 appear to be reliable proliferation
indexes and useful prognostic markers in patients with muscle-invasive
urothelial bladder carcinomas. (c) 2005 Elsevier Inc. All rights
reserved.
ER -