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MammaTyper RT-qPCR 和免疫组织化学检测乳腺癌中 ER、PR、Ki67 和 HER2-低表达的一致性:对临床病理医生的影响。

Concordance between ER, PR, Ki67, and HER2-low expression in breast cancer by MammaTyper RT-qPCR and immunohistochemistry: implications for the practising pathologist.

机构信息

Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.

Department of Pathology, Faculty of Medicine, Menoufia University, Shebin El-Kom, Egypt.

出版信息

Histopathology. 2024 Sep;85(3):437-450. doi: 10.1111/his.15193. Epub 2024 Apr 23.


DOI:10.1111/his.15193
PMID:38651302
Abstract

BACKGROUND: There are limited data on the role of multigene tests and their correlation with immunohistochemistry (IHC), especially on core biopsy. MammaTyper is a quantitative conformite Europeeanne (CE) marked, National Institute for Health and Care excellence (NICE) approved, in in vitro diagnostic quantitative real-time polymerase chain reaction (RT-qPCR) test for assessment of mRNA expression of four biomarkers (ESR1, PGR, ERBB2, MKI67). METHODS: We evaluated the concordance of MammaTyper with oestrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67 by IHC on 133 core needle biopsies of breast cancer. HER2 was positive if IHC 3+ or 2+ and fluorescence in situ hybridization (FISH)-amplified. Global and hotspot Ki67 expression was analysed using a cutoff of ≥20% assessed manually and by digital image analysis. Agreements were expressed as overall percent agreement (OPA), positive percent agreement (PPA), negative percent agreement (NPA), and Cohen's kappa. RESULTS: RT-qPCR results of ESR1 were highly concordant with IHC with OPA of 94.7% using 1% cutoff and 91.7% when the low ER-positive category was included. The PPA and NPA between RT-qPCR and IHC for PR was 91.5% and 88.0%, respectively, when using the 1% cutoff. For ERBB2/HER2, the OPA was 95% and the PPA was 84.6%. 40 of 72 HER2 IHC score 0 tumours were classified as ERBB2 low. Best concordance between MKI67 by MammaTyper and Ki67 IHC was achieved using hotspot digital image analysis (OPA: 87.2%, PPA: 90.6%, NPA: 80%). CONCLUSION: RT-qPCR-based assessment of the mRNA expression of ESR1, PGR, ERBB2, and MKI67 showed high concordance with IHC, suggesting that the MammaTyper test on core needle biopsies represents a reliable, efficient, and reproducible alternative for breast cancer classification and refining HER2 low categorisation.

摘要

背景:关于多基因检测的作用及其与免疫组织化学(IHC)的相关性,尤其是在核心活检中的作用,数据有限。MammaTyper 是一种定量的欧洲合格认证(CE)标记物,经国家卫生与保健卓越研究所(NICE)批准,用于体外诊断定量实时聚合酶链反应(RT-qPCR)检测,以评估四种生物标志物(ESR1、PGR、ERBB2、MKI67)的 mRNA 表达。

方法:我们评估了 MammaTyper 与 133 例乳腺癌核心针活检中的雌激素受体(ER)、孕激素受体(PR)、HER2 和 Ki67 的 IHC 的一致性。如果 IHC 为 3+或 2+且荧光原位杂交(FISH)扩增,则 HER2 为阳性。通过手动和数字图像分析评估≥20%的截断值,分析全局和热点 Ki67 表达。通过总体百分比一致性(OPA)、阳性百分比一致性(PPA)、阴性百分比一致性(NPA)和 Cohen's kappa 表示一致性。

结果:ESR1 的 RT-qPCR 结果与 IHC 高度一致,使用 1%的截断值时 OPA 为 94.7%,包括低 ER 阳性类别时为 91.7%。当使用 1%的截断值时,PR 的 RT-qPCR 和 IHC 之间的 PPA 和 NPA 分别为 91.5%和 88.0%。对于 ERBB2/HER2,OPA 为 95%,PPA 为 84.6%。72 例 HER2 IHC 评分 0 的肿瘤中有 40 例被归类为 ERBB2 低表达。使用热点数字图像分析,MammaTyper 检测的 MKI67 与 Ki67 IHC 之间的最佳一致性(OPA:87.2%,PPA:90.6%,NPA:80%)。

结论:基于 RT-qPCR 的 ESR1、PGR、ERBB2 和 MKI67 mRNA 表达评估与 IHC 高度一致,表明 MammaTyper 检测在核心针活检中代表了一种可靠、高效且可重复的乳腺癌分类替代方法,并可细化 HER2 低分类。

相似文献

[1]
Concordance between ER, PR, Ki67, and HER2-low expression in breast cancer by MammaTyper RT-qPCR and immunohistochemistry: implications for the practising pathologist.

Histopathology. 2024-9

[2]
Comparison of immunohistochemistry and RT-qPCR for assessing ER, PR, HER2, and Ki67 and evaluating subtypes in patients with breast cancer.

Breast Cancer Res Treat. 2022-8

[3]
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BMC Cancer. 2017-2-13

[4]
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Breast. 2024-8

[5]
ESR1, PGR, ERBB2, and MKi67 mRNA expression in postmenopausal women with hormone receptor-positive early breast cancer: results from ABCSG Trial 6.

ESMO Open. 2021-8

[6]
Technical validation of an RT-qPCR in vitro diagnostic test system for the determination of breast cancer molecular subtypes by quantification of ERBB2, ESR1, PGR and MKI67 mRNA levels from formalin-fixed paraffin-embedded breast tumor specimens.

BMC Cancer. 2016-7-7

[7]
Comparison of central laboratory assessments of ER, PR, HER2, and Ki67 by IHC/FISH and the corresponding mRNAs (ESR1, PGR, ERBB2, and MKi67) by RT-qPCR on an automated, broadly deployed diagnostic platform.

Breast Cancer Res Treat. 2018-8-17

[8]
Looking for more reliable biomarkers in breast cancer: Comparison between routine methods and RT-qPCR.

PLoS One. 2021

[9]
Macrodissection prior to closed system RT-qPCR is not necessary for estrogen receptor and HER2 concordance with IHC/FISH in breast cancer.

Lab Invest. 2018-6-1

[10]
Biological subtyping of early breast cancer: a study comparing RT-qPCR with immunohistochemistry.

Breast Cancer Res Treat. 2016-6

引用本文的文献

[1]
Artificial intelligence-assisted HER2 interpretation for breast cancers in a multi-laboratory study.

Gland Surg. 2025-6-30

[2]
HER2-Low Breast Cancer-Current Knowledge and Future Directions.

Medicina (Kaunas). 2025-4-1

[3]
Characterization of SUSD3 as a novel prognostic biomarker and therapeutic target for breast cancer.

Clin Transl Oncol. 2025-3

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