Analyzing historical trends in breast cancer biomarker expression: a feasibility study (1947-2009).
Analyzing historical trends in breast cancer biomarker expression: a feasibility study (1947-2009).
复制标题
DOI：
10.1038/npjbcancer.2015.16
复制
发表时间：
2015
影响因子：
5.9
通讯作者：
Schnitt SJ
中科院分区：
文献类型：
--
作者：
Krieger N;Habel LA;Waterman PD;Shabani M;Ellison-Loschmann L;Achacoso NS;Acton L;Schnitt SJ
确定肿瘤生物标志物表达的长期趋势对于了解肿瘤生物学的变化至关重要。限制了这些数据的可用性，目前使用的生物标志物测定法相对较新。例如，最古老的雌激素受体（ER）检测方法仅可追溯到20世纪70年代。为了扩展对获得肿瘤生物标志物长期数据的可行性的缺乏了解，我们随机选择了1947-2009年间在Kaiser Permanente北方加州健康计划的女性成员中诊断的60例乳腺癌病例（每十年10例），以获得并分析其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。我们定位了60例病例中50例（83%）的肿瘤块和病理报告，从中我们每十年随机抽取5例进行生物标志物分析（n=30）。所有30例病例均表现出良好的形态学，并显示出与组织学类型和分级相符的生物标志物。重测信度也很好：ER为100%;人表皮生长因子受体2和表皮生长因子受体为97%;孕酮受体和细胞角蛋白5/6为93%; Ki 67和分子表型为90%;对于7个生物标志物中的4个，Kappa统计量是极好的（>0.9），对于2个，Kappa统计量是强的（0.6-0.8），并且仅对于1个，Kappa统计量是一般的（由于低流行率）。这些结果表明，通常用于评价乳腺癌生物学和分配替代分子表型的生物标志物的免疫染色可以可靠地用于长达60年的存档FFPE标本。
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. 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. 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). 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.