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

• Verfasst von: Albrecht, Thomas [VerfasserIn]
• Verfasst von: Rausch, Melina [VerfasserIn]
• Verfasst von: Rössler, Stephanie [VerfasserIn]
• Verfasst von: Geissler, Veronika [VerfasserIn]
• Verfasst von: Albrecht, Michael [VerfasserIn]
• Verfasst von: Halske, Christine [VerfasserIn]
• Verfasst von: Seifert, Carolin [VerfasserIn]
• Verfasst von: Renner, Marcus [VerfasserIn]
• Verfasst von: Singer, Stephan [VerfasserIn]
• Verfasst von: Mehrabi, Arianeb [VerfasserIn]
• Verfasst von: Vogel, Monika Nadja [VerfasserIn]
• Verfasst von: Pathil-Warth, Anita [VerfasserIn]
• Verfasst von: Busch, Elena [VerfasserIn]
• Verfasst von: Köhler, Bruno Christian [VerfasserIn]
• Verfasst von: Rupp, Christian [VerfasserIn]
• Verfasst von: Weiss, Karl Heinz [VerfasserIn]
• Verfasst von: Springfeld, Christoph [VerfasserIn]
• Verfasst von: Röcken, Christoph [VerfasserIn]
• Verfasst von: Schirmacher, Peter [VerfasserIn]
• Verfasst von: Goeppert, Benjamin [VerfasserIn]
• Titel: HER2 gene (ERBB2) amplification is a low-frequency driver with potential predictive value in gallbladder carcinoma
• Verf.angabe: 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
• E-Jahr: 2019
• Jahr: 14 December 2019
• Umfang: 10 S.
• Fussnoten: Gesehen am 09.07.2020 ; Band und Seitenzählung momentan nicht zu ermitteln
• Titel Quelle: Enthalten in: Virchows Archiv
• Ort Quelle: Berlin : Springer, 1847
• Jahr Quelle: 2019
• Band/Heft Quelle: 476(2019), Seite 871-880
• ISSN Quelle: 1432-2307
• DOI: doi:10.1007/s00428-019-02706-6
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1693717239

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.