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01.06.2020 | Original Article

HER2 gene (ERBB2) amplification is a low-frequency driver with potential predictive value in gallbladder carcinoma

verfasst von: Thomas Albrecht, Melina Rausch, Stephanie Roessler, Veronika Geissler, Michael Albrecht, Christine Halske, Carolin Seifert, Marcus Renner, Stephan Singer, Arianeb Mehrabi, Monika Nadja Vogel, Anita Pathil-Warth, Elena Busch, Bruno Köhler, Christian Rupp, Karl Heinz Weiss, Christoph Springfeld, Christoph Röcken, Peter Schirmacher, Benjamin Goeppert

Erschienen in: Virchows Archiv | Ausgabe 6/2020

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Abstract

Gallbladder carcinoma (GBC) is an aggressive type of cancer with a dismal prognosis. Recent case reports have highlighted the human epidermal growth factor receptor 2 (HER2) as a promising target for individualized therapy in biliary tract cancer; however, current data on HER2 positivity in GBC is contradictory. This study aimed to assess the proportion of HER2 positivity and its clinical implications in a large and well-characterized European GBC cohort. HER2 status was determined in 186 cases of surgically resected gallbladder adenocarcinoma and a subset of coexistent high-grade biliary intraepithelial neoplasia (BilIN, n = 74) in accordance with the up-to-date consensus for HER2 testing in gastric cancer by immunohistochemistry and dual-color chromogenic in situ hybridization. Positivity for HER2 was observed in 5.4% of all cases (n = 10). In those patients with concomitant high-grade BilIN, two of four positive samples also showed amplification in the precursor lesion, while in the two remaining cases, positivity was either confined to invasive tumor or high-grade BilIN, exclusively. Equivocal staining found in eleven cases was not accompanied by gene amplification. Staging of the HER2-positive group was significantly different from the HER2-negative group with most cases presenting at stage IV, paralleled by a trend towards decreased survival. One patient who received dual HER2 inhibition almost went into full clinical remission despite treatment initiation in a metastasized state. Our results reveal a low prevalence of HER2 positivity and highlight HER2 gene amplification as an early, potentially driving event in gallbladder carcinogenesis. Prospective standardized HER2 testing and randomized control studies are needed to prove clinical efficacy of targeted HER2 inhibition in GBC.

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Titel: HER2 gene (ERBB2) amplification is a low-frequency driver with potential predictive value in gallbladder carcinoma
verfasst von: Thomas Albrecht
Melina Rausch
Stephanie Roessler
Veronika Geissler
Michael Albrecht
Christine Halske
Carolin Seifert
Marcus Renner
Stephan Singer
Arianeb Mehrabi
Monika Nadja Vogel
Anita Pathil-Warth
Elena Busch
Bruno Köhler
Christian Rupp
Karl Heinz Weiss
Christoph Springfeld
Christoph Röcken
Peter Schirmacher
Benjamin Goeppert
Publikationsdatum: 01.06.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Virchows Archiv / Ausgabe 6/2020
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-019-02706-6

Springer Medizin

HER2 gene (ERBB2) amplification is a low-frequency driver with potential predictive value in gallbladder carcinoma

Abstract

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie

Springer Medizin

Abstract

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