用高灵敏度测定法定量测量非小细胞肺癌中的 HER2 表达。

IF 7.1 1区 医学 Q1 PATHOLOGY
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引用次数: 0

摘要

最近,有人提出将 HER2 蛋白的低表达作为预测转移性乳腺癌患者对抗体药物共轭物曲妥珠单抗德鲁司坦(T-DXd)反应的生物标志物。人们从未对非小细胞肺癌(NSCLC)患者的 HER2 表达进行过仔细测量,对未扩增但可检测到该蛋白水平的病例的频率也知之甚少。虽然已经在 NSCLC 患者中研究了一些 HER2 靶向疗法,但这些疗法仅限于有 ERBB2 基因改变的患者,而 ERBB2 基因改变的 NSCLC 病例相对较少。尽管如此,T-DXd 在 NSCLC 中的新兴研究显示,未扩增 HER2 的患者有望接受 T-DXd 治疗。综上所述,我们推测可能会有许多 HER2 蛋白表达水平与乳腺癌相当的 NSCLC 病例从 T-DXd 中获益。在这里,我们使用了一种先前经过验证的定量免疫荧光分析法(QIF),它比传统的临床 HER2 免疫组化分析法更灵敏。我们测量了 NSCLC 病例中的 HER2 蛋白水平,以确定可检测到 HER2 表达的病例比例。使用细胞系校准微阵列和我们的 QIF 方法,我们能够将 HER2 信号转换为每平方毫米阿托摩尔单位。我们发现,在分析的 741 个 NSCLC 病例中,超过 63% 的病例的 HER2 表达超过了检测限,其中超过 17% 的病例超过了定量下限。虽然乳腺癌患者对 T-DXd 的反应阈值尚不清楚,但许多 NSCLC 病例的表达范围与免疫组化评分为 1+ 或 2+ 的乳腺癌病例相当。无论ERBB2基因组是否发生改变,我们的检测方法都有可能筛选出可检测到靶点(即HER2)的NSCLC病例,这些病例可能会从HER2抗体-药物共轭物中获益。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Quantitative Measurement of HER2 Expression in Non–Small Cell Lung Cancer With a High-Sensitivity Assay

Recently, low human epidermal growth factor receptor 2 (HER2) protein expression has been proposed as a predictive biomarker for response to the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) in metastatic breast cancer. HER2 expression in non–small cell lung cancer (NSCLC) patients has never been carefully measured, and little is known about the frequency of cases with unamplified but detectable levels of the protein. Although some HER2-targeted therapies have been studied in NSCLC patients, they have been restricted to those with genomic ERBB2 gene alterations, which only represent relatively rare cases of NSCLC. Still, emerging investigations of T-DXd in NSCLC have shown promise in patients with unamplified HER2. Taken together, we hypothesize that there may be many cases of NSCLC with levels of HER2 protein expression comparable with levels seen in breast cancer that benefit from T-DXd.

Here, we used a previously validated, analytic, quantitative immunofluorescence (QIF) assay that is more sensitive than legacy clinical HER2 immunohistochemistry assays. We measured HER2 protein levels in NSCLC cases to determine the proportion of cases with detectable HER2 expression. Using cell line calibration microarrays alongside our QIF method enabled us to convert HER2 signal into units of attomoles per mm2. We found that over 63% of the 741 analyzed NSCLC cases exhibited HER2 expression above the limit of detection, with more than 17% of them exceeding the lower limit of quantification. Although the threshold for response to T-DXd in breast cancer is still unknown, many cases of NSCLC have expression in a range comparable to breast cancer cases with immunohistochemistry scores of 1+ or 2+. Our assay could potentially select NSCLC cases with a detectable target (ie, HER2) that might benefit from HER2 antibody-drug conjugates, irrespective of ERBB2 genomic alterations.

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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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