Morphological and molecular characteristics of HER2 amplified urothelial bladder cancer.

Tschui, Joëlle; Vassella, Erik; Bandi Hess, Nora; Baumgartner, Ulrich; Genitsch Gratwohl, Vera; Rotzer, Diana; Seiler, Roland; Thalmann, George; Fleischmann, Achim (2015). Morphological and molecular characteristics of HER2 amplified urothelial bladder cancer. Virchows Archiv, 466(6), pp. 703-710. Springer 10.1007/s00428-015-1729-4

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Several (pre-) clinical trials are currently investigating the benefit of HER2-targeted therapy in urothelial bladder cancer (UBC). Patients with HER2 amplified UBC could potentially profit from these therapies. However, little is known about histomorphology, HER2 protein expression patterns and occurrence of alterations in the HER2 gene in their tumors. Among 150 metastasizing primary UBC, 13 HER2 amplified tumors were identified. Their histopathological features were compared with 13 matched, non-amplified UBC. HER2 protein expression was determined by immunohistochemistry. The 26 tumors were screened for mutations in exons 19 and 20 of the HER2 gene. UBC with HER2 amplification presented with a broad variety of histological variants (median 2 vs. 1), frequently featured micropapillary tumor components (77 % vs. 8 %) and demonstrated a high amount of tumor associated inflammation. Immunohistochemically, 10 of 13 (77 %) HER2 amplified tumors were strongly HER2 protein positive. Three tumors (23 %) were scored as HER2 negative. One of the HER2 amplified tumors harbored a D769N mutation in exon 19 of the HER2 gene; all other tested tumors were wild type. In conclusion, HER2 amplified UBC feature specific morphological characteristics. They frequently express the HER2 protein diffusely and are, therefore, promising candidates for HER2 targeted therapies. The detection of mutations at the HER2 locus might add new aspects to molecular testing of UBC.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Other Institutions > Teaching Staff, Faculty of Medicine
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie

UniBE Contributor:

Tschui, Joëlle; Vassella, Erik; Bandi Hess, Nora; Baumgartner, Ulrich; Genitsch Gratwohl, Vera; Rotzer, Diana; Seiler, Roland; Thalmann, George and Fleischmann, Achim

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0945-6317

Publisher:

Springer

Language:

English

Submitter:

Katharina Morgenegg

Date Deposited:

24 Jun 2015 09:16

Last Modified:

10 Sep 2017 16:16

Publisher DOI:

10.1007/s00428-015-1729-4

PubMed ID:

25809292

BORIS DOI:

10.7892/boris.69766

URI:

https://boris.unibe.ch/id/eprint/69766

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