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HER-2/neu、p53及DNA分析作为子宫内膜癌生存预后指标

HER-2/neu, p53, and DNA analyses as prognosticators for survival in endometrial carcinoma.

作者信息

Pisani A L, Barbuto D A, Chen D, Ramos L, Lagasse L D, Karlan B Y

机构信息

Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center/UCLA School of Medicine, USA.

出版信息

Obstet Gynecol. 1995 May;85(5 Pt 1):729-34. doi: 10.1016/0029-7844(95)00037-r.

DOI:10.1016/0029-7844(95)00037-r
PMID:7724103
Abstract

OBJECTIVE

To compare the prognostic importance of certain molecular biologic characteristics (HER-2/neu and p53 gene overexpression, DNA ploidy, and the S-phase fraction) to standard clinical-pathologic factors used to predict survival in patients with endometrial carcinoma.

METHODS

We reviewed archival specimens from 128 patients with endometrial cancer diagnosed during the period 1985-1987. One hundred four cases were eligible for inclusion in the study. Immunohistochemistry was used to detect p53 and HER-2/neu overexpression. We used flow cytometry to calculate DNA ploidy and the S-phase fraction. Life-table analysis and Cox multiple regression were used to analyze clinical and molecular data with respect to survival.

RESULTS

International Federation of Obstetrics and Gynecology stage, nuclear grade, lymph-vascular space invasion, and adverse histopathologic features each significantly correlated with poor outcome (each at P < or = .001). Overexpression of p53 was demonstrated in 15% of the tumors and was associated with a 12% probability of 5-year survival, compared to a 90% probability of 5-year survival for the p53-negative cohort (P = .0001). Thirty percent of the tumors were aneuploid, which was also associated with poor prognosis (P = .0003). HER-2/neu overexpression and an S-phase fraction greater than 10% showed similar trends, but were not statistically significant. On multivariate analysis, p53 overexpression was the strongest independent prognosticator of survival (P = .0001).

CONCLUSION

Molecular characteristics provide objective data that may be useful in predicting prognosis in patients with endometrial cancer. Further investigation of molecular and genetic characteristics are needed to refine our diagnostic and treatment modalities.

摘要

目的

比较某些分子生物学特征(HER-2/neu和p53基因过表达、DNA倍体及S期分数)与用于预测子宫内膜癌患者生存率的标准临床病理因素的预后重要性。

方法

我们回顾了1985年至1987年期间诊断的128例子宫内膜癌患者的存档标本。其中104例符合纳入本研究的条件。采用免疫组织化学检测p53和HER-2/neu过表达。我们使用流式细胞术计算DNA倍体和S期分数。采用寿命表分析和Cox多元回归分析临床和分子数据与生存率的关系。

结果

国际妇产科联合会分期、核分级、淋巴血管间隙浸润及不良组织病理学特征均与不良预后显著相关(均P≤0.001)。15%的肿瘤显示p53过表达,其5年生存率为12%,而p53阴性队列的5年生存率为90%(P = 0.0001)。30%的肿瘤为非整倍体,这也与不良预后相关(P = 0.0003)。HER-2/neu过表达和S期分数大于10%显示出类似趋势,但无统计学意义。多变量分析显示,p53过表达是最强的独立生存预后因素(P = 0.0001)。

结论

分子特征提供了可能有助于预测子宫内膜癌患者预后的客观数据。需要进一步研究分子和遗传特征以完善我们的诊断和治疗方式。

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引用本文的文献

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Genomic imbalances in endometrial adenocarcinomas - comparison of DNA ploidy, karyotyping and comparative genomic hybridization.子宫内膜腺癌中的基因组不平衡——比较 DNA 倍性、核型分析和比较基因组杂交。
Mol Oncol. 2012 Feb;6(1):98-107. doi: 10.1016/j.molonc.2011.10.002. Epub 2011 Oct 20.
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MicroRNA signatures differentiate uterine cancer tumor subtypes.
微小 RNA 特征可区分子宫癌肿瘤亚型。
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Endometrial carcinoma: immunohistochemically detected proliferation index is a prognosticator of long-term outcome.子宫内膜癌:免疫组化检测的增殖指数是长期预后的预测指标。
J Clin Pathol. 1998 Jan;51(1):25-9. doi: 10.1136/jcp.51.1.25.
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Independent prognostic importance of microvessel density in endometrial carcinoma.微血管密度在子宫内膜癌中的独立预后意义。
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