Performance of HER2 DAKO HercepTest and Ventana 4B5 immunohistochemical assays on detecting HER2 gene-amplification in uterine serous carcinomas

IF 2.7 2区医学 Q2 PATHOLOGY

Human pathology Pub Date : 2024-05-11 DOI:10.1016/j.humpath.2024.05.002

Janira M. Navarro Sanchez , Brian S. Finkelman , Haley Tyburski , Bradley M. Turner , Ioana Moisini , Hani Katerji , Sharlin Varghese , Xi Wang , Linda M. Schiffhauer , Jack J. Chen , David G. Hicks , Huina Zhang

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Abstract

We compared the performance of two commonly-used HER2 immunohistochemistry (IHC) assays in uterine serous carcinomas (USC), correlating with HER2 gene amplification by fluorescence in-situ hybridization (FISH). Sixty-five USCs were stained by both HercepTest™ and PATHWAY 4B5 assays. FISH was performed by HER2 IQFISH pharmDx. Consensus HER2 IHC scoring was performed, and HER2 testing results were evaluated using USC-specific criteria. Complete concordance between HercepTest and 4B5 assays was achieved in 44/65 tumors (68%). The overall HER2 IHC/FISH concordance was 94% (45/48) by HercepTest and 91% (42/46) by 4B5. All HER2 IHC 3+ cases with HercepTest (n = 6) and 4B5 (n = 4) were gene-amplified, corresponding to specificities of 100%. For cases with IHC 2+, 41% (7/17) by HercepTest and 42% (8/19) by 4B5 had HER2 gene amplification. The sensitivity for HercepTest and 4B5 were 38% and 25%, respectively, at a cut-off of IHC 3+ (P = 0.50), and were 81% and 75%, respectively, at a cut-off of IHC 2+ (P > 0.99). Among HER2 IHC 0–1+ cases, 3/42 cases by HercepTest and 4/42 cases by 4B5 showed amplified FISH results, corresponding to overall false negative rates of 19% for HercepTest and 25% for 4B5. By using USC-specific IHC scoring criteria, both HercepTest and 4B5 assays showed high specificities (100%) for HER2 gene amplification in IHC 3+ cases, high IHC/FISH concordance, and comparable sensitivity for detecting HER2 gene amplification. The notable false negative rates using IHC 2+ as a cut-off for reflexing FISH analysis may warrant consideration for performing FISH in IHC 1+ cases until more data become available.

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HER2 DAKO HercepTest 和 Ventana 4B5 免疫组化测定在检测子宫浆液性癌中 HER2 基因扩增方面的性能。

我们比较了两种常用的子宫浆液性癌（USC）HER2 免疫组化（IHC）检测方法的性能，并将其与荧光原位杂交（FISH）的 HER2 基因扩增相关联。65 例 USC 采用 HercepTest™ 和 PATHWAY 4B5 检测法进行染色。FISH 由 HER2 IQFISH pharmDx 进行。进行了一致的 HER2 IHC 评分，并使用 USC 特定标准对 HER2 检测结果进行了评估。44/65 例肿瘤（68%）的 HercepTest 和 4B5 检测结果完全一致。HercepTest和4B5检测的HER2 IHC/FISH总吻合率分别为94%（45/48）和91%（42/46）。使用 HercepTest（6 例）和 4B5（4 例）检测的所有 HER2 IHC 3+ 病例均为基因扩增，特异性为 100%。在 IHC 2+ 的病例中，41%（7/17）（HercepTest）和 42%（8/19）（4B5）有 HER2 基因扩增。在 IHC 3+ 临界值时，HercepTest 和 4B5 的灵敏度分别为 38% 和 25% （P=0.50）；在 IHC 2+ 临界值时，灵敏度分别为 81% 和 75% （P>0.99）。在 HER2 IHC 0-1+ 的病例中，3/42（通过 HercepTest 检测）和 4/42 （通过 4B5 检测）的病例出现了扩增的 FISH 结果，相应地，HercepTest 的总体假阴性率为 19%，4B5 的总体假阴性率为 25%。根据 USC 特定的 IHC 评分标准，HercepTest 和 4B5 检测方法对 IHC 3+ 病例中 HER2 基因扩增的特异性都很高（100%），IHC/FISH 的一致性也很高，检测 HER2 基因扩增的灵敏度相当。将 IHC 2+ 作为反射性 FISH 分析的临界值，会出现明显的假阴性率，因此在获得更多数据之前，应考虑在 IHC 1+ 病例中进行 FISH 分析。

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来源期刊

Human pathology 医学-病理学

CiteScore

5.30

自引率

6.10%

发文量

206

审稿时长

21 days

期刊介绍： Human Pathology is designed to bring information of clinicopathologic significance to human disease to the laboratory and clinical physician. It presents information drawn from morphologic and clinical laboratory studies with direct relevance to the understanding of human diseases. Papers published concern morphologic and clinicopathologic observations, reviews of diseases, analyses of problems in pathology, significant collections of case material and advances in concepts or techniques of value in the analysis and diagnosis of disease. Theoretical and experimental pathology and molecular biology pertinent to human disease are included. This critical journal is well illustrated with exceptional reproductions of photomicrographs and microscopic anatomy.