Universität zu Köln

Zinnall, Ulrike, Weyerer, Veronika, Comperat, Eva, Camparo, Philippe, Gaisa, Nadine T., Knuechel-Clarke, Ruth, Perren, Aurel ORCID: 0000-0002-6819-6092, Lugli, Alessandro, Toma, Marieta, Baretton, Gustavo, Kristiansen, Glen, Wirtz, Ralph M., Cheng, Liang, Wullich, Bernd, Stoehr, Robert, Hartmann, Arndt and Bertz, Simone (2018). Micropapillary urothelial carcinoma: evaluation of HER2 status and immunohistochemical characterization of the molecular subtype. Hum. Pathol., 80. S. 55 - 65. PHILADELPHIA: W B SAUNDERS CO-ELSEVIER INC. ISSN 1532-8392

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Abstract

Comprehensive molecular analyses of urothelial bladder cancer (UBC) have defined distinct subtypes with potential therapeutic implications. In this study, we focused on micropapillary urothelial carcinoma (MPUC), an aggressive, histomorphologically defined rare variant. Apart from genetic alterations shared with conventional UBC, alterations of the HER2 gene have been reported in higher frequencies. However, only small cohorts of MPUCs have been analyzed, and the real impact is still unclear. We collected a cohort of 94 MPUCs and immunohistochemically tested HER2, basal (CD44, CK5, EGFR, p63) and luminal (CD24, FOXA1, GATA3, CK20) markers to allocate MPUC to a molecular subtype. Additionally, HER2 amplification status was assigned by chromogenic in situ hybridization. Sanger sequencing of exon 4 and 8 was used to test for HER2 mutations. Kruskal-Wallis test was calculated to compare marker distribution between proportions of the MPUC component. HER2 2+/3+ staining scores were identified in 39.6% of 91 analyzed MPUCs and were not differentially distributed among the proportion of the MPUC component (P = .89). Additionally, CISH analysis revealed 30% of HER2-amplified tumors independently of the MPUC fraction. In 6/90 evaluable MPUCs, a p.S310F HER2 mutation was detected. Overexpression of luminal markers was observed in the majority of MPUC. Our investigations of the largest cohort of analyzed MPUC demonstrate that HER2 overexpression and amplifications are common genetic alterations and identification of overexpressed lumina] markers allows subclassification to the luminal subtype. These findings highlight the need of histomorphological recognition of MPUC and analysis of HER2 status and the luminal molecular subtype for potential targeted therapeutic strategies. (C) 2018 Elsevier Inc. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Zinnall, Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Weyerer, Veronika UNSPECIFIED UNSPECIFIED UNSPECIFIED Comperat, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Camparo, Philippe UNSPECIFIED UNSPECIFIED UNSPECIFIED Gaisa, Nadine T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Knuechel-Clarke, Ruth UNSPECIFIED UNSPECIFIED UNSPECIFIED Perren, Aurel UNSPECIFIED orcid.org/0000-0002-6819-6092 UNSPECIFIED Lugli, Alessandro UNSPECIFIED UNSPECIFIED UNSPECIFIED Toma, Marieta UNSPECIFIED UNSPECIFIED UNSPECIFIED Baretton, Gustavo UNSPECIFIED UNSPECIFIED UNSPECIFIED Kristiansen, Glen UNSPECIFIED UNSPECIFIED UNSPECIFIED Wirtz, Ralph M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cheng, Liang UNSPECIFIED UNSPECIFIED UNSPECIFIED Wullich, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Stoehr, Robert UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Arndt UNSPECIFIED UNSPECIFIED UNSPECIFIED Bertz, Simone UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-171106
DOI:	10.1016/j.humpath.2018.05.022
Journal or Publication Title:	Hum. Pathol.
Volume:	80
Page Range:	S. 55 - 65
Date:	2018
Publisher:	W B SAUNDERS CO-ELSEVIER INC
Place of Publication:	PHILADELPHIA
ISSN:	1532-8392
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INVASIVE BLADDER-CANCER; GENE AMPLIFICATION; URINARY-BLADDER; BREAST-CANCER; VARIANT; OVEREXPRESSION; EXPRESSION; ASSOCIATION; TUMORS Multiple languages Pathology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/17110