title: Preferential HER2 expression in liver metastases and EGFR expression in peritoneal metastases in patients with advanced gastric cancer.
abstract: BACKGROUND
  Despite recent clinical trials, the sensitivity and resistance of metastatic gastric cancer to anti-HER2 and anti-EGFR therapy are still unclear.
  
  
  METHODS
  To clarify the HER2 and EGFR expression status in the metastatic sites, we immunohistochemically compared HER2 and EGFR expression between primary and metastatic tumors from 52 gastric cancer patients with liver metastases and 85 patients with peritoneal metastases.
  
  
  RESULTS
  The HER2 positivity rate of primary and metastatic tumors in patients with liver metastases, especially with intestinal-type histology (70.6 and 80.0 %, respectively), was significantly higher than in primary and metastatic tumors (22.4 and 16.4 %, respectively) in patients with peritoneal metastases. HER2 positivity of the primary tumor and liver metastases showed good concordance (87.5 %) in patients with liver metastases. In contrast, the EGFR positivity rate of metastatic tumors (70.1 %) in patients with peritoneal metastases was significantly higher than that of metastatic tumors (37.5 %) in patients with liver metastases. HER2 and EGFR expression tended to be mutually exclusive, and HER2/EGFR double-positive cases were rare in patients with liver or peritoneal metastases. In four such patients with HER2/EGFR double-positive primary tumors, the HER2- and EGFR-positive areas were separate, and corresponding liver metastasis was only positive for HER2 and peritoneal metastasis only positive for EGFR.
  
  
  CONCLUSIONS
  These results indicate that HER2 and EGFR are preferentially expressed in the liver and peritoneal metastases, respectively, which would be potential targets for anti-HER2 and anti-EGFR molecular therapy in metastatic gastric cancer patients.
authors.affiliation: Program in Health and Community Medicine, Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Saito
authors.affiliation: Division of Oncological Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. hnakanis@aichi-cc.jp.
authors.forename: Hayao
authors.initials: H
authors.lastname: Nakanishi
authors.affiliation: Department of Surgery, Komaki Municipal Hospital, Komaki, Japan.
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Mochizuki
authors.affiliation: Department of Gastroenterological Surgery, Aichi Cancer Center Central Hospital, Nagoya, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Gastroenterological Surgery, Aichi Cancer Center Central Hospital, Nagoya, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Gastroenterological Surgery, Aichi Cancer Center Central Hospital, Nagoya, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Misawa
authors.affiliation: Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Central Hospital, Nagoya, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
authors.affiliation: Department of Surgery, Osaka Saiseikai Izuo Hospital, Osaka, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Yamamichi
authors.affiliation: Program in Health and Community Medicine, Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.|Division of Oncological Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
authors.forename: Eisaku
authors.initials: E
authors.lastname: Kondo
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000556:secondary*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000473:pathology*; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human; C508053:ERBB2 protein, human
keywords: EGFR; Gastric cancer; HER2; Immunohistochemistry; Liver metastases; Molecular targeting therapy; Peritoneal metastases