Trop-2-Expression in soliden Tumoren Erweiterte Proteindiagnostik im Rahmen des Molekularen Tumorboards

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.