Distinct genetic alterations and luminal molecular subtype in nested variant of urothelial carcinoma

Weyerer V, Weisser R, Moskalev E, Haller F, Stöhr R, Eckstein M, Zinnall U, Gaisa NT, Comperat E, Perren A, Keck B, Allory Y, Kristiansen G, Wullich B, Agaimy A, Hartmann A, Bertz S (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Histopathology Wiley

DOI: 10.1111/his.13958

Abstract

Aims Nested variant of urothelial carcinoma (NVUC) is rare, and only a few small series exist. Molecular characteristics and the classifying marker profile as well as therapeutic targets of this specific variant are mostly unknown. The aim of this study was to characterise NVUC at the molecular level in one of the largest cohorts to date. In addition, we applied an immunohistochemical marker panel in order to define the molecular subtype. Methods and results Sixty NVUC cases were collected from different departments. TERT promoter mutation analysis was carried out in all samples using SNaPshot analysis. Targeted sequencing of 48 cancer-related genes by next-generation sequencing (NGS) analysis was performed in a subset of 26 cases. Immunohistochemical markers CD44, CK5, CK14, EGFR, p63, FOXA1, GATA3, CD24 and CK20 were used to elucidate the molecular subtype. A total of 62.5% of NVUC cases harboured a mutation of the TERT promoter. Additionally, TP53, JAK3 and CTNNB1 were among the most frequently mutated genes identified by NGS analysis. Subtyping revealed that all NVUC express luminal markers such as CD24, FOXA1, GATA3 and CK20. Conclusions In summary, NVUC belong to the luminal molecular subtype. Moreover, a subset of NVUC seems to be characterised by mutations of the Wnt and inflammatory pathways, including JAK3 mutations, indicating a different biological background compared to conventional urothelial bladder cancer.

Authors with CRIS profile

Veronika Bahlinger Institute of Pathology Evgeny Moskalev Institute of Pathology Florian Haller Professur für Diagnostische Molekularpathologie Robert Stöhr Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Markus Eckstein Institute of Pathology Bastian Keck Medizinische Fakultät Bernd Wullich Lehrstuhl für Urologie Abbas Agaimy Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Simone Bertz Institute of Pathology

Involved external institutions

Universitätsklinikum Bonn DE Germany (DE) Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen DE Germany (DE) University of Pittsburgh Medical Center (UPMC) US United States (USA) (US) Centre hospitalier universitaire Henri-Mondor (CHU Henri-Mondor) FR France (FR) Universität Bern CH Switzerland (CH)

How to cite

APA:

Weyerer, V., Weisser, R., Moskalev, E., Haller, F., Stöhr, R., Eckstein, M.,... Bertz, S. (2019). Distinct genetic alterations and luminal molecular subtype in nested variant of urothelial carcinoma. Histopathology. https://doi.org/10.1111/his.13958

MLA:

Weyerer, Veronika, et al. "Distinct genetic alterations and luminal molecular subtype in nested variant of urothelial carcinoma." Histopathology (2019).

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