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

TY - JOUR

T1 - 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

AU - Müller, Jan H

AU - Plage, Henning

AU - Elezkurtaj, Sefer

AU - Mandelkow, Tim

AU - Huang, Zhihao

AU - Lurati, Magalie C J

AU - Raedler, Jonas B

AU - Debatin, Nicolaus F

AU - Vettorazzi, Eik

AU - Samtleben, Henrik

AU - Hofbauer, Sebastian

AU - Furlano, Kira

AU - Neymeyer, Jörg

AU - Goranova, Irena

AU - Ralla, Bernhard

AU - Weinberger, Sarah

AU - Horst, David

AU - Roßner, Florian

AU - Schallenberg, Simon

AU - Marx, Andreas H

AU - Fisch, Margit

AU - Rink, Michael

AU - Slojewski, Marcin

AU - Kaczmarek, Krystian

AU - Ecke, Thorsten

AU - Hallmann, Steffen

AU - Koch, Stefan

AU - Adamini, Nico

AU - Lennartz, Maximilian

AU - Minner, Sarah

AU - Simon, Ronald

AU - Sauter, Guido

AU - Zecha, Henrik

AU - Schlomm, Thorsten

AU - Bady, Elena

N1 - Copyright © 2024 Müller, Plage, Elezkurtaj, Mandelkow, Huang, Lurati, Raedler, Debatin, Vettorazzi, Samtleben, Hofbauer, Furlano, Neymeyer, Goranova, Ralla, Weinberger, Horst, Roßner, Schallenberg, Marx, Fisch, Rink, Slojewski, Kaczmarek, Ecke, Hallmann, Koch, Adamini, Lennartz, Minner, Simon, Sauter, Zecha, Schlomm and Bady.

PY - 2024/1

Y1 - 2024/1

N2 - INTRODUCTION: Trophoblast 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.METHODS: To 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.RESULTS: The 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<0.001 each). In pT2-4 carcinomas, the average TROP2 and EpCAM staining intensity was intermediate (61.8±40.9; 18.3±12.3). For both proteins, this was significantly lower than in pTa G2 low grade (p<0.001 each) but also higher than in pTa G3 tumors (p=0.022 for TROP2, p=0.071 for EpCAM). Within pT2-4 carcinomas, the TROP2 and EpCAM staining level was unrelated to pT, grade, UICC-category, and overall or tumor-specific patient survival. The ratio TROP2/EpCAM was unrelated to malignant phenotype and patient prognosis.CONCLUSION: Our data show that TROP2 and EpCAM expression is common and highly interrelated in urothelial neoplasms. Despite of a progressive loss of TROP2/EpCAM during tumor cell dedifferentiation in pTa tumors, the lack of associations with clinicopathological parameters in pT2-4 cancer argues against a major cancer driving role of both proteins for the progression of urothelial neoplasms.

AB - INTRODUCTION: Trophoblast 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.METHODS: To 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.RESULTS: The 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<0.001 each). In pT2-4 carcinomas, the average TROP2 and EpCAM staining intensity was intermediate (61.8±40.9; 18.3±12.3). For both proteins, this was significantly lower than in pTa G2 low grade (p<0.001 each) but also higher than in pTa G3 tumors (p=0.022 for TROP2, p=0.071 for EpCAM). Within pT2-4 carcinomas, the TROP2 and EpCAM staining level was unrelated to pT, grade, UICC-category, and overall or tumor-specific patient survival. The ratio TROP2/EpCAM was unrelated to malignant phenotype and patient prognosis.CONCLUSION: Our data show that TROP2 and EpCAM expression is common and highly interrelated in urothelial neoplasms. Despite of a progressive loss of TROP2/EpCAM during tumor cell dedifferentiation in pTa tumors, the lack of associations with clinicopathological parameters in pT2-4 cancer argues against a major cancer driving role of both proteins for the progression of urothelial neoplasms.

U2 - 10.3389/fonc.2023.1342367

DO - 10.3389/fonc.2023.1342367

M3 - SCORING: Journal article

C2 - 38282671

VL - 13

JO - FRONT ONCOL

JF - FRONT ONCOL

SN - 2234-943X

M1 - 1342367

ER -