Micropapillary urothelial carcinoma: evaluation of HER2 status and immunohistochemical characterization of the molecular subtype

Zinnall U, Weyerer V, Compérat E, Camparo P, Gaisa NT, Knuechel-Clarke R, Perren A, Lugli A, Toma M, Baretton G, Kristiansen G, Wirtz RM, Cheng L, Wullich B, Stoehr R, Hartmann A, Bertz S (2018)

Publication Type: Journal article

Publication year: 2018

Journal

DOI: 10.1016/j.humpath.2018.05.022

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. 2+/3+ HER2 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 luminal markers allows sub-classification 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.

Authors with CRIS profile

Involved external institutions

Universität Bern Switzerland (CH) Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen Germany (DE) Max-Planck-Institut für molekulare Zellbiologie und Genetik / Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) Germany (DE) Centre de Pathologie des Hauts-de-France France (FR) Assistance Publique-Hôpitaux de Paris (AP-HP) France (FR) St. Elisabeth-Krankenhaus Köln-Hohenlind Germany (DE) Universitätsklinikum Bonn Germany (DE) Indiana University – Purdue University Indianapolis United States (USA) (US)

How to cite

APA:

Zinnall, U., Weyerer, V., Compérat, E., Camparo, P., Gaisa, N.T., Knuechel-Clarke, R.,... Bertz, S. (2018). Micropapillary urothelial carcinoma: evaluation of HER2 status and immunohistochemical characterization of the molecular subtype. Human Pathology. https://doi.org/10.1016/j.humpath.2018.05.022

MLA:

Zinnall, Ulrike, et al. "Micropapillary urothelial carcinoma: evaluation of HER2 status and immunohistochemical characterization of the molecular subtype." Human Pathology (2018).

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