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Intra- and Interlaboratory Reproducibility of the Sensitivity to Endocrine Therapy Assay for Stage II/III Breast Cancer
Clinical Chemistry ( IF 9.3 ) Pub Date : 2021-04-29 , DOI: 10.1093/clinchem/hvab068
Veerle Bossuyt 1, 2 , Rosanna Lau 3, 4 , Brandon Young 5 , John Greg Howe 1 , Fengmin Zhao 6 , Brian Leyland-Jones 5 , Lili Du 3 , Tiffany Foli 7 , Christos Hatzis 1 , W Fraser Symmans 3
Affiliation  

Background The sensitivity to endocrine therapy assay (SET2,3) predicts treatment outcomes in Stage II-III breast cancer. SET2,3 measures transcription related to estrogen and progesterone receptors (SETER/PR index) and the molecular subtype (RNA4: ESR1, PGR, ERBB2, AURKA) from formalin-fixed paraffin-embedded (FFPE) tissue sections. Methods We designed a nested study across 3 pathology laboratories, each testing 60 breast cancers twice in controlled batches. Laboratories macrodissected and directly homogenized the unstained FFPE tumor sections, then performed the QuantiGene Plex bead-based hybridization assay. SET2,3 was calculated centrally using predefined statistical R-scripts and applying pre-defined cutpoints. Concordance correlation coefficient (CCC) was calculated from continuous measurements and Kappa statistic from categorical results. A mixed-effects model estimated contributions to bias (fixed effects) and variance (random effects) from the replicated design. Results Intralaboratory (CCC 0.96–0.99) and interlaboratory (CCC 0.98–0.99) SET2,3 results were concordant, with rates of agreement for high/low categorization within (Kappa 0.83–0.93) and between laboratories (Kappa 0.87–0.88). The relative contributions to overall variance of SET2,3 measurements were 96.90% from biological differences between cancers, 0.67% from interlaboratory variability, and 2.44% from residual causes including intralaboratory replicates. Similar results were obtained with SETER/PR, the baseline prognostic index calculated using pathological or clinical tumor and nodal staging information, and the 4 individual genes (ESR1, PGR, ERBB2, and AURKA). Conclusion Intra- and interpathology laboratory measurements of SET2,3 and its components were highly reproducible when tested from FFPE tumor sections.

中文翻译:

II/III 期乳腺癌内分泌治疗敏感性试验的实验室内和实验室间可重复性

背景 对内分泌治疗分析 (SET2,3) 的敏感性可预测 II-III 期乳腺癌的治疗结果。SET2,3 测量福尔马林固定石蜡包埋 (FFPE) 组织切片中与雌激素和孕激素受体(SETER/PR 指数)和分子亚型(RNA4:ESR1、PGR、ERBB2、AURKA)相关的转录。方法 我们设计了一项跨 3 个病理学实验室的嵌套研究,每个实验室在受控批次中检测 60 例乳腺癌两次。实验室对未染色的 FFPE 肿瘤切片进行宏观解剖和直接均质化,然后进行基于 QuantiGene Plex 珠的杂交测定。SET2,3 是使用预定义的统计 R 脚本和应用预定义的切点集中计算的。一致性相关系数 (CCC) 从连续测量和分类结果的 Kappa 统计中计算。混合效应模型估计重复设计对偏差(固定效应)和方差(随机效应)的贡献。结果 实验室内 (CCC 0.96–0.99) 和实验室间 (CCC 0.98–0.99) SET2,3 结果是一致的,在 (Kappa 0.83–0.93) 和实验室之间 (Kappa 0.87–0.88) 的高/低分类一致率。SET2,3 测量值对总体方差的相对贡献为 96.90% 来自癌症之间的生物学差异,0.67% 来自实验室间变异性,2.44% 来自包括实验室内重复在内的残留原因。使用 SETER/PR、使用病理或临床肿瘤和淋巴结分期信息计算的基线预后指数以及 4 个单独的基因(ESR1、PGR、ERBB2 和 AURKA)获得了类似的结果。
更新日期:2021-04-29
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