Aneuploidy Predicts Outcome in Patients with Endometrial Carcinoma and Is Related to Lack of CDH13 Hypermethylation
Aneuploidy Predicts Outcome in Patients with Endometrial Carcinoma and Is Related to Lack of CDH13 Hypermethylation
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DOI：
10.1158/1078-0432.ccr-07-4609
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发表时间：
2008-06
影响因子：
11.5
通讯作者：
Y. Suehiro;T. Okada;Takae Okada;K. Anno;N. Okayama;Koji Ueno;Mikako Hiura;Mikiko Nakamura;T. K
中科院分区：
文献类型：
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作者：
Y. Suehiro;T. Okada;Takae Okada;K. Anno;N. Okayama;Koji Ueno;Mikako Hiura;Mikiko Nakamura;T. K
目的：许多研究者报道了流式细胞术检测非整倍体是子宫内膜癌患者的一个有用的预后指标。激光扫描细胞术（LSC）是一种类似于流式细胞术的技术，但更适合临床实验室使用。我们评估了LSC检测DNA倍体作为子宫内膜癌患者预后标志物的有效性，并研究了与非整倍体相关的遗传和表观遗传因素。实验设计：对106例子宫内膜癌患者的标本进行评估。研究了CDH13、Rassf1、SFRP1、SFRP2、SFRP4、SFRP5、p16、hMLH1、MGMT、APC、ATM和WIF1基因的甲基化状态以及p53和CDC4基因的突变。采用LSC法测定DNA倍性。荧光原位杂交用染色体特异性着丝粒探针来评估染色体的不稳定性。结果：单因素和多因素分析显示p53突变和缺乏CDH13高甲基化与非整倍体呈正相关。单因素分析显示，非整倍体、染色体不稳定性、缺乏CDH13高甲基化以及手术分期是子宫内膜癌死亡的显著预测因素。此外，多变量分析显示，合并DNA非整倍体或缺乏CDH13高甲基化的阶段是一个独立的预后因素。结论：分析CDH13的DNA倍体和甲基化状态可能有助于预测子宫内膜癌患者的临床预后。需要前瞻性随机试验来证实个体化方法的有效性，包括确定肿瘤倍体和CDH13的甲基化状态，以管理子宫内膜癌患者。
Purpose: Many investigators have reported that aneuploidy detected by flow cytometry is a useful prognostic marker in patients with endometrial cancer. Laser scanning cytometry (LSC) is a technology similar to flow cytometry but is more feasible for clinical laboratory use. We evaluated the usefulness of DNA ploidy detected by LSC as a prognostic marker in patients with endometrial cancer and investigated genetic and epigenetic factors related to aneuploidy. Experimental Design: Endometrial cancer specimens from 106 patients were evaluated. The methylation status of CDH13, Rassf1, SFRP1, SFRP2, SFRP4, SFRP5, p16, hMLH1, MGMT, APC, ATM, and WIF1 and mutations in the p53 and CDC4 genes were investigated. LSC was carried out to determine DNA ploidy. Fluorescence in situ hybridization was done with chromosome-specific centromeric probes to assess chromosomal instability. Results: Univariate and multivariate analyses revealed that p53 mutation and lack of CDH13 hypermethylation associated positively with aneuploidy. Univariate analysis showed that aneuploidy, chromosomal instability, and lack of CDH13 hypermethylation as well as surgical stage were significantly predictive of death from endometrial cancer. Furthermore, multivariate analysis revealed that stage in combination with either DNA aneuploidy or lack of CDH13 hypermethylation was an independent prognostic factor. Conclusion: These results suggest that analysis of DNA ploidy and methylation status of CDH13 may help predict clinical outcome in patients with endometrial cancer. Prospective randomized trials are needed to confirm the validity of an individualized approach, including determination of tumor ploidy and methylation status of CDH13, to management of endometrial cancer patients.