Universität zu Köln

Schnitzler, Tician, Ortiz-Bruechle, Nadina, Schneider, Ursula, Lurje, Isabella, Guricova, Karolina, Buchner, Alexander ORCID: 0000-0001-7895-7070, Schulz, Gerald Bastian, Heidenreich, Axel, Gaisa, Nadine Therese, Knuechel, Ruth and Garczyk, Stefan (2020). Pure high-grade papillary urothelial bladder cancer: a luminal-like subgroup with potential for targeted therapy. Cell. Oncol., 43 (5). S. 807 - 820. DORDRECHT: SPRINGER. ISSN 2211-3436

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Abstract

Purpose Non-invasive high-grade (HG) bladder cancer is a heterogeneous disease that is characterized insufficiently. First-line Bacillus Calmette-Guerin instillation fails in a substantial amount of cases and alternative bladder-preserving treatments are limited, underlining the need to promote a further molecular understanding of non-invasive HG lesions. Here, we characterized pure HG papillary urothelial bladder cancer (pure pTa HG), a potential subgroup of non-invasive HG bladder carcinomas, with regard to molecular subtype affiliation and potential for targeted therapy. Methods An immunohistochemistry panel comprising luminal (KRT20, ERBB2, ESR2, GATA3) and basal (KRT5/6, KRT14) markers as well as p53 and FGFR3 was used to analyze molecular subtype affiliations of 78 pure pTa HG/papillary pT1(a) HG samples. In 66 of these, ERBB2 fluorescence in situ hybridization was performed. Additionally, targeted sequencing (31 genes) of 19 pTa HG cases was conducted, focusing on known therapeutic targets or those described to predict response to targeted therapies noted in registered clinical trials or that are already approved. Results We found that pure pTa HG/papillary pT1(a) HG lesions were characterized by a luminal-like phenotype associated with frequent (58% of samples) moderate to high ERBB2 protein expression, rare FGFR3 alterations on genomic and protein levels, and a high frequency (89% of samples) of chromatin-modifying gene alterations. Of note, 95% of pTa HG/papillary pT1 HG cases harbored at least one potential druggable genomic alteration. Conclusions Our data should help guiding the selection of targeted therapies for investigation in future clinical trials and, additionally, may provide a basis for prospective mechanistic studies of pTa HG pathogenesis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schnitzler, Tician UNSPECIFIED UNSPECIFIED UNSPECIFIED Ortiz-Bruechle, Nadina UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneider, Ursula UNSPECIFIED UNSPECIFIED UNSPECIFIED Lurje, Isabella UNSPECIFIED UNSPECIFIED UNSPECIFIED Guricova, Karolina UNSPECIFIED UNSPECIFIED UNSPECIFIED Buchner, Alexander UNSPECIFIED orcid.org/0000-0001-7895-7070 UNSPECIFIED Schulz, Gerald Bastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Heidenreich, Axel UNSPECIFIED UNSPECIFIED UNSPECIFIED Gaisa, Nadine Therese UNSPECIFIED UNSPECIFIED UNSPECIFIED Knuechel, Ruth UNSPECIFIED UNSPECIFIED UNSPECIFIED Garczyk, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-333106
DOI:	10.1007/s13402-020-00524-6
Journal or Publication Title:	Cell. Oncol.
Volume:	43
Number:	5
Page Range:	S. 807 - 820
Date:	2020
Publisher:	SPRINGER
Place of Publication:	DORDRECHT
ISSN:	2211-3436
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CARCINOMA IN-SITU; DNA-DAMAGE; BREAST-CANCER; SURVIVAL; MUTATION; PROGRESSION; DEFICIENCY; EXPRESSION; SUBTYPES; REPAIR Multiple languages Oncology; Cell Biology; Pathology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33310