Universität zu Köln

Kessler, Carolina, von Brandenstein, Melanie ORCID: 0000-0002-1499-7644, Klümper, Niklas, Krausewitz, Philipp, Storz, Enno ORCID: 0009-0002-8250-5522, Rieger, Constantin ORCID: 0009-0000-3993-7974, Sperber, Laurenz, Paffenholz, Pia ORCID: 0000-0002-8209-7795, Tolkach, Yuri ORCID: 0000-0001-5239-2841, Wirtz, Ralph, Eckstein, Markus, Heidenreich, Axel ORCID: 0000-0002-2511-3664 and Weiten, Richard ORCID: 0009-0002-7216-1033 (2025). TROP-2 overexpression in papillary renal cell carcinoma supports its potential as a therapeutic target for antibody-drug-conjugate therapy. World Journal of Urology, 43 (1). pp. 1-8. Springer Nature. ISSN 1433-8726

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Abstract

[Artikel-Nr.: 522] Objective: To evaluate the expression of trophoblast cell surface antigen-2 (TROP-2), a broadly expressed antibody-drug conjugate (ADC) target, in non-clear cell renal cell carcinoma (nccRCC), and to perform a proof-of-concept analysis assessing the cytotoxic efficacy of the TROP-2-directed ADC Sacituzumab govitecan (SG) in RCC cell lines. Methods: A cohort comprising clear cell RCC (ccRCC, n = 44), papillary (pRCC, n = 22), chromophobe (chRCC, n = 22), and benign renal tumors (n = 8, including oncocytoma and angiomyolipoma) was analysed using reverse transcription quantitative PCR (RT-qPCR), immunohistochemistry (IHC) with H-score quantification, and enzyme-linked immunosorbent assay (ELISA). In RCC cell lines, TROP-2 protein levels were assessed by Western blotting and flow cytometry, and SG cytotoxicity was evaluated using MTT assays. Results: TROP-2 mRNA levels were significantly elevated in pRCC compared to ccRCC, chRCC and benign renal tumors (p < 0.001). IHC revealed moderate to strong membranous TROP-2 expression in most pRCC cases [n = 20/22 with H-score ≥ 100, median H-score 265 (IQR 202.5–290)], while TROP-2 expression was absent or weak in ccRCC and chRCC (p < 0.0001). Soluble TROP-2 was detectable in patient serum of RCC patients and strongly correlated with tissue expression (ρ = 0.78, p = 0.0001, R2 = 0.52). In vitro, TROP-2-positive Caki-1 cells exhibited significant growth inhibition after SG treatment, whereas TROP-2-negative 769-P cells showed resistance (p < 0.01). Conclusion: The selective overexpression of TROP-2 in pRCC, and its functional relevance demonstrated in vitro, provide compelling preclinical evidence supporting TROP-2 as a therapeutic target. These findings support further investigation of TROP-2-directed ADCs, such as SG, in patients with metastatic TROP-2-positive pRCC.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Kessler, Carolina UNSPECIFIED UNSPECIFIED UNSPECIFIED von Brandenstein, Melanie UNSPECIFIED https://orcid.org/0000-0002-1499-7644 UNSPECIFIED Klümper, Niklas UNSPECIFIED UNSPECIFIED UNSPECIFIED Krausewitz, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Storz, Enno UNSPECIFIED https://orcid.org/0009-0002-8250-5522 UNSPECIFIED Rieger, Constantin UNSPECIFIED https://orcid.org/0009-0000-3993-7974 UNSPECIFIED Sperber, Laurenz UNSPECIFIED UNSPECIFIED UNSPECIFIED Paffenholz, Pia UNSPECIFIED https://orcid.org/0000-0002-8209-7795 UNSPECIFIED Tolkach, Yuri UNSPECIFIED https://orcid.org/0000-0001-5239-2841 UNSPECIFIED Wirtz, Ralph UNSPECIFIED UNSPECIFIED UNSPECIFIED Eckstein, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Heidenreich, Axel UNSPECIFIED https://orcid.org/0000-0002-2511-3664 UNSPECIFIED Weiten, Richard UNSPECIFIED https://orcid.org/0009-0002-7216-1033 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-810912
Identification Number:	10.1007/s00345-025-05880-2
Journal or Publication Title:	World Journal of Urology
Volume:	43
Number:	1
Page Range:	pp. 1-8
Number of Pages:	8
Date:	1 September 2025
Publisher:	Springer Nature
ISSN:	1433-8726
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Pathologie und Neuropathologie > Institut für Pathologie Faculty of Medicine > Urologie > Klinik und Poliklinik für Urologie
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language Antibody-drug conjugates · Renal cell carcinoma · Sacituzumab govitecan · TROP-2 English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81091