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低 cdc27 和高 securin 表达预示乳腺癌患者的生存时间短。

Low cdc27 and high securin expression predict short survival for breast cancer patients.

机构信息

Department of Pathology, University Hospital of Turku, Turku, Finland.

出版信息

APMIS. 2013 Oct;121(10):945-53. doi: 10.1111/apm.12110. Epub 2013 Jun 12.

Abstract

Cell cycle regulators cdc27 and securin participate in control of the mitotic checkpoint and survey the mitotic spindle to maintain chromosomal integrity. This is achieved by their functions in metaphase-anaphase transition, DNA damage repair, enhancement of mitotic arrest and apoptosis. We report on the roles of cdc27 and securin in aneuploidy and prognosis of breast cancer. The study comprises 429 breast cancer patients with up to 22 years of follow-up. DNA content was determined by image cytometry, and immunopositivity for cdc27 and securin was based on tissue microarrays. An inverse association between cdc27 and securin expression was observed in both image cytometric and immunohistochemical analyses. Low cdc27 and high securin expression identified patients with significant difference in disease outcome. Cdc27 and securin immunoexpression identified patients at risk of early cancer death within five years from diagnosis. In multivariate analysis, the combination of cdc27 and securin immunohistochemistry was the strongest predictor of cancer death after lymph node status. We demonstrate, for the first time in human breast cancer, the prognostic value of cdc27 and securin immunohistochemistry. Cdc27 and securin appear promising biomarkers for applications in predicting disease progression, prognostication of individual patients and potential in anti-mitotic drug development.

摘要

细胞周期调控因子 cdc27 和 securin 参与有丝分裂检查点的控制,并对纺锤体进行检测以维持染色体的完整性。它们在中期-后期转化、DNA 损伤修复、增强有丝分裂阻滞和细胞凋亡方面发挥作用来实现这一点。我们报告了 cdc27 和 securin 在乳腺癌非整倍体和预后中的作用。该研究包括 429 名接受长达 22 年随访的乳腺癌患者。通过图像细胞术测定 DNA 含量,基于组织微阵列测定 cdc27 和 securin 的免疫阳性率。在图像细胞术和免疫组化分析中均观察到 cdc27 和 securin 表达呈负相关。低 cdc27 和高 securin 表达的患者疾病结局存在显著差异。cdc27 和 securin 免疫表达鉴定出了在诊断后五年内有早期癌症死亡风险的患者。在多变量分析中,cdc27 和 securin 免疫组化的组合是淋巴结状态后癌症死亡的最强预测因子。我们首次在人类乳腺癌中证明了 cdc27 和 securin 免疫组化的预后价值。cdc27 和 securin 似乎是有前途的生物标志物,可用于预测疾病进展、预测个别患者的预后以及在抗有丝分裂药物开发方面的潜力。

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