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Background <p>Trophoblast surface antigen&#xa0;2 (Trop-2) is a&#xa0;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.</p> Methods <p>The pan-cancer cohort examined comprises 50&#xa0;patients from the Comprehensive Cancer Center Freiburg who were enrolled in the MTB and additionally received a&#xa0;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&#xa0;tissue samples and used for correlation analysis with IHC expression levels.</p> Results <p>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&#xa0;positive correlation with MS-based protein intensities (Pearson correlation coefficient&#xa0;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%.</p> Discussion <p>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.</p>

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Trop-2-Expression in soliden Tumoren

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月27日

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

摘要

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.