Optimizing flow cytometric DNA ploidy and S-phase fraction as independent prognostic markers for node-negative breast cancer specimens

Optimizing flow cytometric DNA ploidy and S-phase fraction as independent prognostic markers for node-negative breast cancer specimens
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DOI:
10.1002/cyto.1097
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发表时间:
2001-06-15
期刊:
CYTOMETRY
影响因子:
--
通讯作者:
Baldetorp, B
Baldetorp, B
中科院分区:
其他
文献类型:
--
作者:
Bagwell, CB;Clark, GM;Baldetorp, B

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开发一个可靠的和定量的评估恶性肿瘤的潜在毒力一直是一个长期的目标,在临床细胞计数,DNA直方图分析提供了有价值的信息,通过S期估计的肿瘤群体的循环活动,它也确定非二倍体人群,遗传不稳定性和随后的易感性转移的可能指标。由于文献中相互矛盾的研究,这两个潜在的预后标志物的临床相关性已被质疑乳腺癌患者的管理。本研究的目的是提供一组10项调整,这些调整来自一项大型研究,该研究优化了DNP、倍性和S期的预后强度,并在另外两项大型多中心研究中测试该方法的有效性。根据贝勒学院的单个淋巴结阴性乳腺癌数据库开发了对DNA倍性和S期的十项调整(n = 961例病例),根据非整倍体分数和DNA指数最佳阈值,其中7个调整用于将直方图重新分类为低风险和高风险倍性模式,导致预后P值从很小的变化,来自瑞典(n = 210例)和法国(n = 220例)的其他数据库显示了类似的DNA倍体改善预后意义,分别为P < 0.02至P < 0.0009和P < 0.12至P <0.002。对二倍体和非整倍体S期进行了其他三种调整,这些调整消除了DNA倍性和S期之间的虚假相关性,并使它们能够独立地联合收割机成为一个强大的预后模型,能够将患者分为低、中、高风险组(P < 0.000005),当Baylor预后模型应用于瑞典和法国数据库时,观察到相似的显著患者分层(分别为P < 0.0003和P < 0.00001)。贝勒预后模型的成功转移到其他研究表明,建议的调整可能会发挥重要作用,在标准化这个测试,并提供有价值的预后信息,参与管理乳腺癌患者。(C)2001 Wiley-Liss,Inc.
Developing a reliable and quantitative assessment of the potential virulence of a malignancy has been a long-standing goal in clinical cytometry, DNA histogram analysis provides valuable information on the cycling activity of a tumor population through S-phase estimates; it also identifies nondiploid populations, a possible indicator of genetic instability and subsequent predisposition to metastasis. Because of conflicting studies in the literature, the clinical relevance of both of these potential prognostic markers has been questioned for the management of breast cancer patients. The purposes of this study are to present a set of 10 adjustments derived from a single large study that optimizes the prognostic strength of both DNP, ploidy and S-phase and to test the validity of this approach on two other large multicenter studies. Ten adjustments to both DNA ploidy and S-phase were developed from a single node-negative breast cancer database from Baylor College (n = 961 cases), Seven of the adjustments were used to reclassify histograms into low-risk and high-risk ploidy patterns based on aneuploid fraction and DNA index optimum thresholds resulting in prognostic P values changing from little (P < 0.02) or no significance to P < 0.000005, Other databases from Sweden (n = 210 cases) and France (n = 220 cases) demonstrated similar improvement of DNA ploidy prognostic significance, P < 0.02 to P < 0.0009 and P < 0.12 to P < 0,002, respectively. Three other adjustments were applied to diploid and aneuploid S-phases, These adjustments eliminated a spurious correlation between DNA ploidy and S-phase and enabled them to combine independently into a powerful prognostic model capable of stratifying patients into low, intermediate, and high-risk groups (P < 0.000005), When the Baylor prognostic model was applied to the Sweden and French databases, similar significant patient stratifications were observed (P < 0.0003 and P < 0.00001, respectively). The successful transference of the Baylor prognostic model to other studies suggests that the proposed adjustments may play an important role in standardizing this test and provide valuable prognostic information to those involved in the management of breast cancer patients. (C) 2001 Wiley-Liss, Inc.