학술논문
Loss of TROP2 and epithelial cell adhesion molecule expression is linked to grade progression in pTa but unrelated to disease outcome in pT2-4 urothelial bladder carcinomas
Document Type
article
Author
Jan H. Müller; Henning Plage; Sefer Elezkurtaj; Tim Mandelkow; Zhihao Huang; Magalie C. J. Lurati; Jonas B. Raedler; Nicolaus F. Debatin; Eik Vettorazzi; Henrik Samtleben; Sebastian Hofbauer; Kira Furlano; Jörg Neymeyer; Irena Goranova; Bernhard Ralla; Sarah Weinberger; David Horst; Florian Roßner; Simon Schallenberg; Andreas H. Marx; Margit Fisch; Michael Rink; Marcin Slojewski; Krystian Kaczmarek; Thorsten Ecke; Steffen Hallmann; Stefan Koch; Nico Adamini; Maximilian Lennartz; Sarah Minner; Ronald Simon; Guido Sauter; Henrik Zecha; Thorsten Schlomm; Elena Bady
Source
Frontiers in Oncology, Vol 13 (2024)
Subject
Language
English
ISSN
2234-943X
Abstract
IntroductionTrophoblast cell surface antigen 2 (TROP2; EpCAM2) is a transmembrane glycoprotein which is closely related to EpCAM (EpCAM; EpCAM1). Both proteins share partial overlapping functions in epithelial development and EpCAM expression but have not been comparatively analyzed together in bladder carcinomas. TROP2 constitutes the target for the antibody-drug conjugate Sacituzumab govitecan (SG; TrodelvyTM) which has been approved for treatment of metastatic urothelial carcinoma by the United States Food and Drug administration (FDA) irrespective of its TROP2 expression status. MethodsTo evaluate the potential clinical significance of subtle differences in TROP2 and EpCAM expression in urothelial bladder cancer, both proteins were analyzed by multiplex fluorescence immunohistochemistry in combination with a deep-learning based algorithm for automated cell detection on more than 2,700 urothelial bladder carcinomas in a tissue microarray (TMA) format. ResultsThe staining pattern of TROP2 and EpCAM were highly similar. For both proteins, the staining intensity gradually decreased from pTa G2 low grade (TROP2: 68.8±36.1; EpCAM: 21.5±11.7) to pTa G2 high grade (64.6±38.0; 19.3±12.2) and pTa G3 (52.1±38.7; 16.0±13.0, p