Comparison of HER2 status between surgically resected specimens and matched biopsy specimens of gastric intestinal-type adenocarcinoma.

HER2 protein overexpression and gene amplification are important biomarkers for identifying gastric cancer patients who may respond to HER2-targeted therapy using trastuzumab. The aim of this study was to evaluate the concordance between HER2 protein expression and gene amplification in both surgica...

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Publicado en:Virchows Archiv: European Journal of Pathology Vol. 465; no. 2; pp. 145 - 155
Autores principales: Yoshida, Hiroshi, Yamamoto, Noriko, Taniguchi, Hirokazu, Oda, Ichiro, Katai, Hitoshi, Kushima, Ryoji, Tsuda, Hitoshi
Formato: research Journal Article
Publicado: Springer Nature Aug2014
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Aug2014
      vid: 465
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      pub: Springer Nature
      place: New York, New York
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        atl: Comparison of HER2 status between surgically resected specimens and matched biopsy specimens of gastric intestinal-type adenocarcinoma.
      aug:
        au:
          Yoshida, Hiroshi
          Yamamoto, Noriko
          Taniguchi, Hirokazu
          Oda, Ichiro
          Katai, Hitoshi
          Kushima, Ryoji
          Tsuda, Hitoshi
        affil: Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
      sug:
        subj:
          Adenocarcinoma Metabolism
          Adenocarcinoma Pathology
          Receptors, Cell Surface Metabolism
          Stomach Neoplasms Metabolism
          Stomach Neoplasms Pathology
          Tumor Markers, Biological Metabolism
          Adenocarcinoma Surgery
          Adult
          Aged
          Aged, 80 and Over
          Biopsy
          Surgery, Digestive System
          Female
          Gene Amplification
          Genes
          Genetics
          Human
          Immunohistochemistry
          In Situ Hybridization, Fluorescence
          Male
          Middle Age
          Receptors, Cell Surface
          Stomach Neoplasms Surgery
          Tumor Markers, Biological
          Biochemical Phenomena
          Adult: 19-44 years
          Aged: 65+ years
          Aged, 80 & over
          Middle Aged: 45-64 years
          Female
          Male
      ab: HER2 protein overexpression and gene amplification are important biomarkers for identifying gastric cancer patients who may respond to HER2-targeted therapy using trastuzumab. The aim of this study was to evaluate the concordance between HER2 protein expression and gene amplification in both surgically resected tumors and matched biopsy specimens of gastric cancer. Formalin-fixed, paraffin-embedded sections of 207 surgically resected tumors and 158 biopsy specimens from 207 cases of invasive intestinal-type gastric cancer were analyzed. Protein expression was assessed using immunohistochemistry and graded by the modified scoring criteria for gastric cancer. Gene amplification was evaluated by fluorescence in situ hybridization (FISH). HER2 overexpression was observed in 17 % of both surgically resected tumors (35/207) and biopsy specimens (26/158). HER2 gene amplification was detected in 31 % (61/200) of surgically resected tumors and 32 % (47/147) of biopsy specimens. Except for immunohistochemistry (IHC) equivocal (2+) cases, the concordance rates between IHC and FISH was 90.9 % in surgically resected tumors and 90.2 % in biopsy specimens. In IHC 2+ cases, the rate of HER2 gene amplification was 56 and 38 % in surgically resected tumors and biopsy specimens, respectively. IHC-FISH discordance was mainly due to intratumoral heterogeneity and low-level gene amplification. The concordance rate of IHC results between surgically resected specimens and the corresponding biopsy specimen was 57.0 % (κ = 0.224), and in discordant cases, HER2 positivity in biopsies and HER2 negativity in surgically resected tumors were most common. The concordance rate of FISH results between surgically resected tumors and biopsy specimens was 72.7 % (κ = 0.313). Polysomy 17 was detected in 5.5 and 7.5 % of surgically resected tumors and biopsy specimens and significantly correlated with IHC score, but polysomy 17 could explain one IHC score 3+ and FISH-negative tumor only. Although high concordance rates between HER2-protein expression and gene amplification were observed in both surgically resected tumors and biopsy specimens, the agreement levels were evaluated to be fair. Polysomy 17 was infrequent and seemed to have limited impact on gastric HER2 testing. Further investigations are required for an appropriate biopsy method to reduce false results of HER2 testing and to clarify the clinical significance of intratumoral heterogeneity in HER2 status.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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