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Acquired microsatellite instability status and loss of HER2 positivity during treatment of gastro-esophageal junction adenocarcinoma

  • Lynn Gabrielle Alexis
    Affiliations
    Department of Medical Oncology, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain (UCLouvain), Brussels, Belgium
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  • Hélène Dano
    Affiliations
    Department of Pathology, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain (UCLouvain), Brussels, Belgium
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  • Anne-France Dekairelle
    Affiliations
    Department of Genetics, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain (UCLouvain), Brussels, Belgium
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  • Author Footnotes
    ⁎ These authors contributed equally to this work.
    Cédric Van Marcke
    Footnotes
    ⁎ These authors contributed equally to this work.
    Affiliations
    Department of Medical Oncology, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain (UCLouvain), Brussels, Belgium
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  • Author Footnotes
    ⁎ These authors contributed equally to this work.
    Marc Van den Eynde
    Correspondence
    Corresponding author: Cliniques universitaires Saint-Luc, Avenue Hippocrate, 10 - 1200 Brussels - Belgium.
    Footnotes
    ⁎ These authors contributed equally to this work.
    Affiliations
    Department of Medical Oncology and Hepato-Gastroenterology, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain (UCLouvain), Brussels, Belgium
    Search for articles by this author
  • Author Footnotes
    ⁎ These authors contributed equally to this work.
Published:December 26, 2022DOI:https://doi.org/10.1016/j.dld.2022.11.023
      Gastro-oesophageal adenocarcinomas (GOAs) are a common cause of cancer mortality worldwide. Nowadays, beyond histological classification, the management of GOAs depends on molecular classification. The Cancer Genome Atlas consortium identified four different molecular subtypes of GOAs potentially allowing to tailor the treatment strategies [
      Cancer Genome Atlas Research Network
      Analysis Working Group: asan University, BC Cancer Agency, et al. Integrated genomic characterization of oesophageal carcinoma.
      ]. About 20% of patients show an overexpression or amplification of the Human Epidermal Growth Factor Receptor-2 (HER2). These tumors are generally microsatellite stable (MSS) and present chromosomal instability [
      Cancer Genome Atlas Research Network
      Analysis Working Group: asan University, BC Cancer Agency, et al. Integrated genomic characterization of oesophageal carcinoma.
      ]. The anti-HER2 monoclonal antibody trastuzumab combined with platinum and fluoropyrimidine chemotherapy is the standard first line regimen for these patients [
      • Lordick F.
      • Carneiro F.
      • Cascinu S.
      • et al.
      Gastric cancer: ESMO Clinical practice guideline for diagnosis, treatment and follow-up.
      ]. Microsatellite instable (MSI) and DNA mismatch repair deficient (dMMR) cancers are a distinct subtype of GOAs with a prevalence of up to ∼20% and being more frequent in early stage [
      • Puliga E.
      • Corso S.
      • Pietrantonio F.
      • et al.
      Microsatellite instability in gastric cancer: between lights and shadows.
      ]. These tumors are often associated with a hypermutated phenotype resulting in extensive formation of cancer-specific neoantigens triggering robust anti-cancer immune responses. They benefit extensively from anti-PD-1 immune checkpoint blockade [
      • Lordick F.
      • Carneiro F.
      • Cascinu S.
      • et al.
      Gastric cancer: ESMO Clinical practice guideline for diagnosis, treatment and follow-up.
      ,
      • Chao J.
      • Fuchs C.S.
      • Shitara K.
      • et al.
      Assessment of pembrolizumab therapy for the treatment of microsatellite instability-high gastric or gastroesophageal junction cancer among patients in the KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 clinical trials.
      ]. Here, we describe a rare case of acquisition of MSI and the concomitant loss of HER2 positivity potentially due to selective therapeutic pressure in a metastatic MSS GOA treated with platinum-based chemotherapy and trastuzumab.

      Keywords

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