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- Title
Minichromosome maintenance proteins 2 and 5 in non-benign epithelial ovarian tumours: relationship with cell cycle regulators and prognostic implications.
- Authors
Gakiopoulou, H.; Korkolopoulou, P.; Levidou, G.; Thymara, I.; Saetta, A.; Piperi, C.; Givalos, N.; Vassilopoulos, I.; Ventouri, K.; Tsenga, A.; Bamias, A.; Dimopoulos, M.-A.; Agapitos, E.; Patsouris, E.
- Abstract
Minichromosome maintenance proteins (MCM) have recently emerged as novel proliferation markers with prognostic implications in several tumour types. This is the first study investigating MCM-2 and MCM-5 immunohistochemical expression in a series of ovarian adenocarcinomas and low malignant potential (LMP) tumours aiming to determine possible associations with clinicopathological parameters, the conventional proliferation index Ki-67, cell cycle regulators (p53, p27Kip1, p21WAF1 and pRb) and patients’ outcome. Immunohistochemistry was applied in a series of 43 cases of ovarian LMP tumours and 85 cases of adenocarcinomas. Survival analysis was restricted to adenocarcinomas. The median MCM-2 and MCM-5 labelling indices (LIs) were significantly higher in adenocarcinomas compared to LMP tumours (P<0.0001 for both associations). In adenocarcinomas, the levels of MCM-2 and MCM-5 increased significantly with advancing tumour stage (P=0.0052 and P=0.0180, respectively), whereas both MCM-2 and MCM-5 increased significantly with increasing tumour grade (P=0.0002 and P=0.0006, respectively) and the presence of bulky residual disease (P<0.0001 in both relationships). A strong positive correlation was established between MCM-2 or MCM-5 expression level and Ki-67 LI (P<0.0001) as well as p53 protein (P=0.0038 and P=0.0500, respectively). Moreover, MCM-2 LI was inversely correlated with p27Kip−1 LI (P=0.0068). Finally, both MCM-2 and MCM-5 were associated significantly with adverse patients’ outcome in both univariate (20 vs >20%, P=0.0011 and 25 vs <25%, P=0.0100, respectively) and multivariate (P=0.0001 and 0.0090, respectively) analysis. An adequately powered independent group of 45 patients was used in order to validate our results in univariate survival analysis. In this group, MCM-2 and MCM-5 expression retained their prognostic significance (P<0.0001 in both relationships). In conclusion, MCM-2 and MCM-5 proteins appear to be promising as prognostic markers in patients with ovarian adenocarcinomas.British Journal of Cancer (2007) 97, 1124–1134. doi:10.1038/sj.bjc.6603992 www.bjcancer.com Published online 16 October 2007
- Subjects
OVARIAN cancer; CANCER patients; ADENOCARCINOMA; ONCOLOGY; MEDICAL research
- Publication
British Journal of Cancer, 2007, Vol 97, Issue 8, p1124
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/sj.bjc.6603992