Expression of the potential therapeutic target claudin-18.2 is frequently decreased in gastric cancer: results from a large Caucasian cohort study.

Gastric cancer (GC) is frequently diagnosed and treated in advanced tumour stages with poor prognosis. Recent studies have identified isoform 2 of the tight junction protein claudin-18 (CLDN18.2) as a promising target in GC therapy. In this study, we aimed to outline the expression of CLDN18.2 and i...

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Publicado en:Virchows Archiv: European Journal of Pathology Vol. 475; no. 5; pp. 563 - 572
Autores principales: Dottermusch, Matthias, Krüger, Sandra, Behrens, Hans-Michael, Halske, Christine, Röcken, Christoph
Formato: pictorial research tables/charts Journal Article
Publicado: Springer Nature Nov2019
Acceso en línea:Ver este registro en EBSCOhost
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      place: New York, New York
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        atl: Expression of the potential therapeutic target claudin-18.2 is frequently decreased in gastric cancer: results from a large Caucasian cohort study.
      aug:
        au:
          Dottermusch, Matthias
          Krüger, Sandra
          Behrens, Hans-Michael
          Halske, Christine
          Röcken, Christoph
        affil: Department of Pathology, Christian-Albrechts-University, Arnold-Heller-Str. 3, Haus 14, 24105, Kiel, Germany
      sug:
        subj:
          Stomach Neoplasms Metabolism
          Membrane Proteins Metabolism
          Glycoside Hydrolases Metabolism
          Aged
          Immunohistochemistry
          Proteins Metabolism
          Prognosis
          Female
          White Persons
          Neoplasm Staging
          Cell Membrane Pathology
          Prospective Studies
          Stomach Neoplasms Pathology
          Stomach Neoplasms Diagnosis
          Phenotype
          Male
          Human
          Aged: 65+ years
          Female
          Male
      ab: Gastric cancer (GC) is frequently diagnosed and treated in advanced tumour stages with poor prognosis. Recent studies have identified isoform 2 of the tight junction protein claudin-18 (CLDN18.2) as a promising target in GC therapy. In this study, we aimed to outline the expression of CLDN18.2 and its correlation with clinico-pathological patient characteristics in a large and well-characterized cohort of GC patients. The expression of CLDN18.2 was studied in 481 GCs by immunohistochemistry on whole tissue sections. Immunostained GCs were evaluated using the histoscore (H-score) and subsequently divided into two groups: tumours showing any or no expression. CLDN18.2 expression was investigated for correlation with various clinico-pathological patient characteristics, including survival. CLDN18.2 expression was found in 203 GCs (42.2%). Of these tumours, 71 (14.8%) showed solely weak immunostaining. CLDN18.2 expression correlated with mucin phenotype, EBV status, the integrin αvβ5, the EpCAM extracellular domain EpEX, and lysozyme. We found no correlation with survival, Laurén phenotype, or any other clinico-pathological patient characteristic. In conclusion, we demonstrate frequently decreased expression of CLDN18.2 in a GC cohort of appropriate size. Correlating CLDN18.2 expression with clinico-pathological patient characteristics reveals new linkages to αvβ5, EpEX, and lysozyme, which may pave the way for further investigations regarding the role of tight junction proteins in GC progression. Though CLDN18.2 continues to pose an attractive target candidate, we conclude that a rather low overall expression rate challenges its significance in advanced GC therapy and indicates the need for further investigations across different populations.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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