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Analyzing historical trends in breast cancer biomarker expression: a feasibility study (1947-2009).
npj Breast Cancer ( IF 6.5 ) Pub Date : 2016-01-26 , DOI: 10.1038/npjbcancer.2015.16
Nancy Krieger 1 , Laurel A Habel 2 , Pamela D Waterman 1 , Melina Shabani 3 , Lis Ellison-Loschmann 4 , Ninah S Achacoso 2 , Luana Acton 2 , Stuart J Schnitt 3
Affiliation  

BACKGROUND/OBJECTIVES Determining long-term trends in tumor biomarker expression is essential for understanding aspects of tumor biology amenable to change. Limiting the availability of such data, currently used assays for biomarkers are relatively new. For example, assays for the estrogen receptor (ER), which are the oldest, extend back only to the 1970s. METHODS To extend scant knowledge about the feasibility of obtaining long-term data on tumor biomarkers, we randomly selected 60 breast cancer cases (10 per decade) diagnosed between 1947-2009 among women members of the Kaiser Permanente Northern California health plan to obtain and analyze their formalin-fixed paraffin-embedded (FFPE) tumor specimens. For each tumor specimen, we created duplicate tissue microarrays for analysis. RESULTS We located tumor blocks and pathology reports for 50 of the 60 cases (83%), from which we randomly sampled 5 cases per decade for biomarker analysis (n = 30). All 30 cases displayed excellent morphology and exhibited biomarkers compatible with histologic type and grade. Test-retest reliability was also excellent: 100% for ER; 97% for human epidermal growth factor receptor 2 and epidermal growth factor receptor; 93% for progesterone receptor and cytokeratin 5/6; and 90% for Ki67 and molecular phenotype; the kappa statistic was excellent (>0.9) for 4 of the 7 biomarkers, strong (0.6-0.8) for 2, and fair for only 1 (owing to low prevalence). CONCLUSIONS These results indicate immunostaining for biomarkers commonly used to evaluate breast cancer biology and assign surrogate molecular phenotypes can reliably be employed on archival FFPE specimens up to 60 years old.

中文翻译:

分析乳腺癌生物标志物表达的历史趋势:一项可行性研究(1947-2009年)。

背景/目的确定肿瘤生物标志物表达的长期趋势对于理解易于改变的肿瘤生物学方面至关重要。限制了此类数据的可用性,目前使用的生物标志物检测方法相对较新。例如,最古老的雌激素受体(ER)分析仅可追溯到1970年代。方法为了扩大对获取肿瘤生物标志物长期数据的可行性的了解,我们从北加州凯泽永久医疗计划的女性中随机选择了1947年至2009年之间确诊的60例乳腺癌病例(每十年10例),以进行分析。他们的福尔马林固定石蜡包埋(FFPE)肿瘤标本。对于每个肿瘤标本,我们创建了重复的组织微阵列用于分析。结果我们在60例病例中的50例(83%)中找到了肿瘤块和病理报告,从中我们每十年随机抽取5例样本进行生物标志物分析(n = 30)。所有30例均表现出优异的形态,并显示出与组织学类型和等级相容的生物标志物。重测可靠性也非常好:ER为100%; ER为100%。人表皮生长因子受体2和表皮生长因子受体的比例为97%;孕激素受体和细胞角蛋白5/6为93%;Ki67和分子表型占90%;7种生物标志物中有4种的kappa统计值极好(> 0.9),有2种的kappa统计值很强(0.6-0.8),只有1种是公平的(由于低患病率)。
更新日期:2019-11-01
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