Author:
Zschäbitz Stefanie,Mikuteit Marie,Stöhr Christine,Herrmann Edwin,Polifka Iris,Agaimy Abbas,Trojan Lutz,Ströbel Philipp,Becker Frank,Wülfing Christian,Barth Peter,Stöckle Michael,Staehler Michael,Stief Christian,Haferkamp Axel,Hohenfellner Markus,Duensing Stefan,Macher-Göppinger Stephan,Wullich Bernd,Noldus Joachim,Brenner Walburgis,Roos Frederik C.,Walter Bernhard,Otto Wolfgang,Burger Maximilian,Schrader Andres Jan,Hartmann Arndt,Erlmeier Franziska,Steffens Sandra
Abstract
Abstract
Background
Nectin-4 contributes to tumor proliferation, lymphangiogenesis and angiogenesis in malignant tumors and is an emerging target in tumor therapy. In renal cell carcinoma (RCC) VEGF-directed tyrosine kinase inhibitors and checkpoint inhibitors are currently treatments of choice. Enfortumab vedotin-ejf (EV) is an antibody drug conjugate that targets Nectin-4. The aim of our study was to investigate the expression of Nectin-4 in a large cohort of papillary RCC specimens.
Patients and methods
Specimens were derived from the PANZAR consortium (Erlangen, Heidelberg, Herne, Homburg, Mainz, Mannheim, Marburg, Muenster, LMU Munich, TU Munich, and Regensburg). Clinical data and tissue samples from n = 190 and n = 107 patients with type 1 and 2 pRCC, respectively, were available. Expression of Nectin-4 was determined by immunohistochemistry (IHC).
Results
In total, Nectin-4 staining was moderately or strongly positive in of 92 (48.4%) of type 1 and 39 (36.4%) type 2 of pRCC cases. No associations between Nectin-4 expression and age at diagnosis, gender, grading, and TNM stage was found. 5 year overall survival rate was not statistically different in patients with Nectin-4 negative versus Nectin-4 positive tumors for the overall cohort and the pRCC type 2 subgroup, but higher in patient with Nectin-4 positive pRCC type 1 tumors compared to Nectin-4 negative tumors (81.3% vs. 67.8%, p = 0.042).
Conclusion
Nectin-4 could not be confirmed as a prognostic marker in pRCC in general. Due to its high abundance on pRCC specimens Nectin-4 is an interesting target for therapeutical approaches e.g. with EV. Clinical trials are warranted to elucidate its role in the pRCC treatment landscape.
Funder
Deutsche Forschungsgemeinschaft
Deutsche Gesellschaft für Urologie
Medizinische Hochschule Hannover (MHH)
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Endocrine and Autonomic Systems,Endocrinology,Oncology,Endocrinology, Diabetes and Metabolism
Cited by
2 articles.
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