Evidence map›Paper›PMID 38282671›Full record

ArticleFrontiers in oncology2023

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.

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 and 25 more

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Article in Frontiers in oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

35 authors.

Jan H MüllerInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Henning PlageDepartment of Urology, Charité Berlin, Berlin, Germany.
Sefer ElezkurtajDepartment of Urology, Charité Berlin, Berlin, Germany.
Tim MandelkowInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Zhihao HuangInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Magalie C J LuratiInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Jonas B RaedlerInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Nicolaus F DebatinInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Eik VettorazziDepartment of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Henrik SamtlebenDepartment of Urology, Charité Berlin, Berlin, Germany.
Sebastian HofbauerDepartment of Urology, Charité Berlin, Berlin, Germany.
Kira FurlanoDepartment of Urology, Charité Berlin, Berlin, Germany.
Jörg NeymeyerDepartment of Urology, Charité Berlin, Berlin, Germany.
Irena GoranovaDepartment of Urology, Charité Berlin, Berlin, Germany.
Bernhard RallaDepartment of Urology, Charité Berlin, Berlin, Germany.
Sarah WeinbergerDepartment of Urology, Charité Berlin, Berlin, Germany.
David HorstInsitute of Pathology, Charité Berlin, Berlin, Germany.
Florian RoßnerInsitute of Pathology, Charité Berlin, Berlin, Germany.
Simon SchallenbergInsitute of Pathology, Charité Berlin, Berlin, Germany.
Andreas H MarxDepartment of Pathology, Academic Hospital Fuerth, Fuerth, Germany.
Margit FischDepartment of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Michael RinkDepartment of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Marcin SlojewskiDepartment of Urology, University Hospital Stettin, Stettin, Poland.
Krystian KaczmarekDepartment of Urology, University Hospital Stettin, Stettin, Poland.
Thorsten EckeDepartment of Urology, Helios Hospital Bad Saarow, Bad Saarow, Germany.
Steffen HallmannDepartment of Urology, Helios Hospital Bad Saarow, Bad Saarow, Germany.
Stefan KochDepartment of Pathology, Helios Hospital Bad Saarow, Bad Saarow, Germany.
Nico AdaminiDepartment of Urology, Albertinen Hospital, Hamburg, Germany.
Maximilian LennartzInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Sarah MinnerInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Ronald SimonInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Guido SauterInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Henrik ZechaDepartment of Urology, Albertinen Hospital, Hamburg, Germany.
Thorsten SchlommDepartment of Urology, Charité Berlin, Berlin, Germany.
Elena BadyInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

bladder cancerEpCAMmultiplex fluorescence immunohistochemistrymuscle invasive urothelial cancerTROP2

Identifiers

PMID38282671
PMCPMC10811247

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