开发和验证具有高度观察者间一致性的 HER2 低度聚焦 IHC 评分系统 澳大利亚 HER2 低度乳腺癌一致性研究。

IF 7.1 1区 医学 Q1 PATHOLOGY
Gelareh Farshid , Jane Armes , Benjamin Dessauvagie , Amardeep Gilhotra , Beena Kumar , Hema Mahajan , Ewan Millar , Nirmala Pathmanathan , Cameron Snell
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引用次数: 0

摘要

DESTINY Breast-04 试验(DB-04)显示,曲妥珠单抗地屈孕酮对患有转移性 HER2 低乳腺癌(1+ 或 2+ IHC,无扩增)的女性患者具有生存优势。虽然DB-04采用了2018 ASCO CAP HER2 IHC评分标准,但IHC评分的主观性和不精确性引起了人们对患者治疗可能存在误区的担忧。我们小组由 9 位经验丰富的乳腺病理学家组成,整理了一组来自 3 个实验室的 60 例乳腺癌核心活检组织的去标识化数据,使用 Ventana 4B5 HER2 检测仪进行评估,大部分局部评分为 HER2 0 或 1+。根据 ASCO CAP 2018 标准和我们在报告 HER2 IHC 方面的丰富经验,我们为 HER2 蛋白表达水平较低的癌症制定了评分规范,并阐明了具体的评分陷阱。然后,每位病理学家查看 IHC 切片的数字化全片图像,并对每个病例的 HER2 表达进行评分。在随后的共识研讨会上,我们共同审查了病例,以便 i) 为每个病例确定共识评分;ii) 确定 HER2 表达肿瘤细胞的百分比。我们就所有病例达成了共识,其中 40 例归类为 1+,3 例归类为 2+(未扩增),共计 43 例(71.7%)HER2 低表达癌症。93.3%的病例(60 例中的 56 例)的共识评分与病理学家独立评分的多数意见一致。在 17 例(41.2%)局部报告为 HER2 0 的病例中,有 7 例被归类为 HER2 低。相反,在 32 例局部评分为 1+ 的病例中,有 7 例(21.8%)被重新分类为超低或无效。病理学家个人匹配共识评分的准确率为 73.3%-91.67%(平均 80.74%)。在 HER2 低度癌症中,小于 20% 的肿瘤细胞表达 HER2 的一致性水平最低。4名观察者的一致性科恩卡帕系数为优、1名观察者为良、4名观察者为中。这组具有专家共识 HER2 评分的病例参考资料对于同行培训和发展我们针对 HER2 低的癌症的国家外部质量保证计划非常有价值。在评估HER2蛋白表达量较低的乳腺癌时,我们有针对性的评分标准和明确的误区指导提高了病理学家的准确性和一致性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Development and Validation of a HER2-Low Focused Immunohistochemical Scoring System With High-Interobserver Concordance: The Australian HER2-Low Breast Cancer Concordance Study

The DESTINY Breast-04 trial revealed survival advantages of trastuzumab deruxtecan for women with metastatic HER2-low breast cancer (1+ or 2+ immunohistochemistry [IHC], without amplification). Although this trial applied the 2018 Americal Society of Clinial Oncology (ASCO)/College of American Pathologists (CAP) HER2 IHC scoring criteria, the subjectivity and imprecision in IHC scoring have raised concerns that patients’ treatment may be misaligned. Our group of 9 experienced breast pathologists collated a deidentified set of 60 breast cancer core biopsies from 3 laboratories, evaluated with the Ventana 4B5 HER2 assay and mostly scored locally as HER2 0 or 1+. Based on ASCO/CAP 2018 criteria and our extensive experience of reporting HER2 IHC, we specified scoring conventions for cancers with low levels of HER2 protein expression, articulating specific scoring pitfalls. Each pathologist then reviewed digitized whole slide images of the IHC slides and scored the HER2 expression for each case. At a subsequent consensus workshop, we reviewed the cases jointly to establish consensus scores for each case and determine the percentage of HER2 expressing tumor cells. Consensus was reached on all cases, with 40 classified as 1+ and 3 as 2+ (not amplified), totaling 43 (71.7%) HER2-low cancers. The remaining cases were HER2 0. In 93.3% of cases (56/60), the consensus score matched with the majority opinion of pathologists’ independent scores. Seven (41.2%) of the 17 cases reported locally as HER2 0 were classified as HER2 low. Conversely, among 32 cases with local scores of 1+, 7 (21.8%) were reclassified as ultralow or null. Individual pathologists’ accuracy in matching the consensus scores ranged from 73.3% to 91.67% (mean, 80.74%). Among HER2-low cancers those in which <20% of the tumor cells expressed HER2 had the lowest concordance levels. Observers Cohen’s κ coefficients for concordance were excellent for 4, good in 1, and moderate in the 4 observers. This reference set of cases with expert consensus HER2 scores will be invaluable for peer training and development of our national external quality assurance program for HER2-low cancers. For assessing breast cancers at the low end of HER2 protein expression, our targeted scoring criteria and explicit instruction on pitfalls improved pathologists’ accuracy and concordance.

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来源期刊
Modern Pathology
Modern Pathology 医学-病理学
CiteScore
14.30
自引率
2.70%
发文量
174
审稿时长
18 days
期刊介绍: Modern Pathology, an international journal under the ownership of The United States & Canadian Academy of Pathology (USCAP), serves as an authoritative platform for publishing top-tier clinical and translational research studies in pathology. Original manuscripts are the primary focus of Modern Pathology, complemented by impactful editorials, reviews, and practice guidelines covering all facets of precision diagnostics in human pathology. The journal's scope includes advancements in molecular diagnostics and genomic classifications of diseases, breakthroughs in immune-oncology, computational science, applied bioinformatics, and digital pathology.
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