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

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 c...

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Publicado en:Virchows Archiv: European Journal of Pathology Vol. 476; no. 6; pp. 871 - 881
Autores principales: Albrecht, Thomas, Rausch, Melina, Roessler, Stephanie, Geissler, Veronika, Albrecht, Michael, Halske, Christine, Seifert, Carolin, Renner, Marcus, Singer, Stephan, Mehrabi, Arianeb, Vogel, Monika Nadja, Pathil-Warth, Anita, Busch, Elena, Köhler, Bruno, Rupp, Christian, Weiss, Karl Heinz, Springfeld, Christoph, Röcken, Christoph, Schirmacher, Peter, Goeppert, Benjamin
Formato: Journal Article
Publicado: Springer Nature Jun2020
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Jun2020
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s00428-019-02706-6
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        atl: HER2 gene (ERBB2) amplification is a low-frequency driver with potential predictive value in gallbladder carcinoma.
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          Albrecht, Thomas
          Rausch, Melina
          Roessler, Stephanie
          Geissler, Veronika
          Albrecht, Michael
          Halske, Christine
          Seifert, Carolin
          Renner, Marcus
          Singer, Stephan
          Mehrabi, Arianeb
          Vogel, Monika Nadja
          Pathil-Warth, Anita
          Busch, Elena
          Köhler, Bruno
          Rupp, Christian
          Weiss, Karl Heinz
          Springfeld, Christoph
          Röcken, Christoph
          Schirmacher, Peter
          Goeppert, Benjamin
        affil: Institute of Pathology, Heidelberg University Hospital, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany
      sug:
        subj:
          Adenocarcinoma Diagnosis
          Receptors, Cell Surface
          Gallbladder Neoplasms Diagnosis
          Prospective Studies
          Female
          Aged
          Gallbladder Neoplasms
          Middle Age
          Germany
          Male
          Prognosis
          Aged, 80 and Over
          Gallbladder Neoplasms Pathology
          Adenocarcinoma
          In Situ Hybridization
          Adenocarcinoma Pathology
          Predictive Value of Tests
          Immunohistochemistry
          Gene Amplification
          Scales
          Aged: 65+ years
          Middle Aged: 45-64 years
          Aged, 80 & over
          Female
          Male
      ab: 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.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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