Minichromosome maintenance proteins 2 and 5 in non-benign epithelial ovarian tumours: relationship with cell cycle regulators and prognostic implications.
Minichromosome maintenance proteins 2 and 5 in non-benign epithelial ovarian tumours: relationship with cell cycle regulators and prognostic implications.
复制标题
非固定上皮卵巢肿瘤中的微小浓度维持蛋白2和5：与细胞周期调节剂和预后意义的关系。
DOI：
10.1038/sj.bjc.6603992
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发表时间：
2007-10-22
影响因子：
8.8
通讯作者：
Patsouris, E
中科院分区：
文献类型：
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作者：
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
微小染色体维持蛋白（MCM）最近出现作为新的增殖标志物与预后的影响，在几种肿瘤类型。这是第一项研究MCM-2和MCM-5的免疫组化表达在一系列卵巢腺癌和低恶性潜能（LMP）肿瘤，旨在确定可能的关联与临床病理参数，传统的增殖指数Ki-67，细胞周期调节因子（p53，p27 Kip 1，p21 WAF 1和pRb）和患者的结果。应用免疫组化法对43例卵巢LMP肿瘤和85例腺癌进行了研究。生存分析仅限于腺癌。腺癌中MCM-2和MCM-5标记指数（LI）的中位数显著高于LMP肿瘤（两种相关性均P<0.0001）。在腺癌中，MCM-2和MCM-5的水平随着肿瘤分期的进展而显著增加（分别为P=0.0052和P=0.0180），而MCM-2和MCM-5均随着肿瘤分级的增加（分别为P=0.0002和P=0.0006）和大体积残留病变的存在而显著增加（两种关系中P<0.0001）。MCM-2和MCM-5表达水平与Ki-67 LI（P<0.0001）和p53蛋白表达水平（分别为P=0.0038和P=0.0500）呈正相关。此外，MCM-2 LI与p27 Kip −1 LI呈负相关（P=0.0068）。最后，MCM-2和MCM-5在单变量分析（分别为20 vs > 20%，P=0.0011和25 vs <25%，P =0.0100）和多变量分析（分别为P=0.0001和0.0090）中均与不良患者结局显著相关。为了验证我们在单变量生存分析中的结果，我们使用了一个有足够把握度的45例独立组。在该组中，MCM-2和MCM-5表达保持其预后意义（两种关系均P<0.0001）。总之，MCM-2和MCM-5蛋白似乎是有前途的卵巢腺癌患者的预后标志物。
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.