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[实体瘤中的Trop-2表达:分子肿瘤委员会内扩展的蛋白质诊断]

[Trop-2 expression in solid tumors : Expanded protein diagnostics within the molecular tumor board].

作者信息

Dopfer Elaine-Pashupati, Fahrner Matthias, Thiery Johanna, Riemer Cysar Stepan, Heyer Jannis, Bronsert Peter, Becker Heiko, Kuehn Julia C, Lowinus Theresa, Gräßel Linda, Rawluk Justyna, Boerries Melanie, Barsch Maryam, Quante Michael, Peters Christoph, Duyster Justus, Schultheis Anne, Werner Martin, Miething Christoph Cornelius, Schilling Oliver, Timme-Bronsert Sylvia

机构信息

Institut für Klinische Pathologie, Universitätsklinikum Freiburg, Breisacher Str. 115a, 79106, Freiburg, Deutschland.

Comprehensive Cancer Center Freiburg (CCCF), Medizinische Fakultät, Universitätsklinikum Freiburg, Freiburg, Deutschland.

出版信息

Pathologie (Heidelb). 2025 Jun 27. doi: 10.1007/s00292-025-01441-x.

Abstract

BACKGROUND

Trophoblast surface antigen 2 (Trop-2) is a surface antigen that can be targeted by novel antibody-drug conjugates (ADCs). Here we report on the systematic evaluation of Trop‑2 expression and the determination of the biomarker in solid tumors as part of expanded protein diagnostics within the molecular tumor board (MTB) in Freiburg.

METHODS

The pan-cancer cohort examined comprises 50 patients from the Comprehensive Cancer Center Freiburg who were enrolled in the MTB and additionally received a Trop‑2 IHC staining that was performed using formalin-fixed and paraffin-embedded tissue samples. Utilizing the H‑score, the samples were categorized into negative-, low-, moderate-, or high-expressing tumors. Additionally, mass spectrometry (MS)-based proteomics was performed on 22 tissue samples and used for correlation analysis with IHC expression levels.

RESULTS

Trop‑2 expression was negative in 16%, low in 20%, moderate in 18%, and high in 46% of the assessed cases. The Trop‑2 IHC scores showed a positive correlation with MS-based protein intensities (Pearson correlation coefficient 0.48). Treatment recommendation for Trop‑2 ADC was given in 61% and Trop‑2 ADC was considered as the best therapeutic option in 20%.

DISCUSSION

The evaluation of Trop‑2 expression might be helpful for personalized treatment recommendations in the off-label setting as well as ranking strategies for personalized therapeutic options within the MTB. The positive correlation between Trop‑2 IHC scores and MS-based protein intensities validates the IHC and demonstrates the promise of multi-omics assessment of therapeutic biomarkers.

摘要

背景

滋养层表面抗原2(Trop-2)是一种表面抗原,可被新型抗体药物偶联物(ADC)靶向。在此,我们报告了对Trop-2表达的系统评估以及实体瘤中生物标志物的测定,这是弗莱堡分子肿瘤委员会(MTB)内扩展蛋白质诊断的一部分。

方法

所检查的泛癌队列包括来自弗莱堡综合癌症中心的50名患者,他们参加了MTB,并额外接受了使用福尔马林固定和石蜡包埋组织样本进行的Trop-2免疫组化染色。利用H评分,将样本分为低表达、中度表达或高表达肿瘤。此外,对22个组织样本进行了基于质谱(MS)的蛋白质组学分析,并用于与免疫组化表达水平的相关性分析。

结果

在评估的病例中,16%的Trop-2表达为阴性,20%为低表达,18%为中度表达,46%为高表达。Trop-2免疫组化评分与基于MS的蛋白质强度呈正相关(Pearson相关系数为0.48)。61%的病例给出了Trop-2 ADC的治疗建议,20%的病例认为Trop-2 ADC是最佳治疗选择。

讨论

Trop-2表达的评估可能有助于在标签外治疗中进行个性化治疗推荐,以及在MTB内为个性化治疗选择制定排序策略。Trop-2免疫组化评分与基于MS的蛋白质强度之间的正相关验证了免疫组化,并证明了对治疗生物标志物进行多组学评估的前景。

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