Article Text

Download PDFPDF
HER2 is frequently overexpressed in hepatoid adenocarcinoma and gastric carcinoma with enteroblastic differentiation: a comparison of 35 cases to 334 gastric carcinomas of other histological types
  1. Masakazu Fujimoto1,
  2. Ibu Matsuzaki1,
  3. Masaru Nishino1,
  4. Yoshifumi Iwahashi1,
  5. Kenji Warigaya1,
  6. Fumiyoshi Kojima1,
  7. Kazuo Ono2,
  8. Shin-Ichi Murata1
  1. 1 Department of Diagnostic Pathology, Wakayama Medical University, Wakayama, Japan
  2. 2 Department of Diagnostic Pathology, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan
  1. Correspondence to Dr Shin-Ichi Murata, Department of Diagnostic Pathology, Wakayama Medical University, Wakayama 641-8510, Japan; smurata{at}


Aims α-Fetoprotein (AFP)-producing gastric carcinoma (AFPGC) is one of the most aggressive GC subtypes. Frequent expression of human epidermal growth factor receptor 2 (HER2) has previously been reported in hepatoid adenocarcinoma (HAC), a major histological subtype of AFPGC originating from common-type GC (CGC). However, HER2 expression levels in other AFPGC histological subtypes are unknown. In this study, we analysed HER2 expression in GCs with primitive phenotypes in addition to HAC.

Methods HER2 expression was evaluated in representative complete sections from 16 HACs, 19 GCs with enteroblastic differentiation (GCEDs) and 334 GCs of other histological types as controls. The Ruschoff/Hofmann method was used to score HER2 immunohistochemistry. Samples with a HER2 score of 2+ were further assessed using fluorescence in situ hybridisation. Oncofetal protein (OFP) expression in HAC and GCED was tested via immunohistochemical staining for AFP, glypican 3 and Sal-like protein 4.

Results Thirty of 35 HAC/GCED cases comprised more than two histological patterns. The HER2 positivity rates of each histological component in the HACs/GCEDs were 25.0% for HAC (n=16), 34.6% for GCED (n=26) and 48.1% for CGC (n=27), which were higher than those of the control group (13.8%). Additionally, the majority of CGC components in HACs/GCEDs were positive for OFP (88.9%).

Conclusions HER2 is frequently overexpressed not only in HAC but also in GCED and CGC components of HACs/GCEDs, which suggests an association between HER2 and OFP expression. Moreover, our findings suggest that HER2-positive CGC has a higher risk of progression to HAC/GCED than HER2-negative GC.

  • gastric
  • gastric cancer
  • gastric pathology
  • gut pathology

Statistics from


  • Handling editor Runjan Chetty.

  • Competing interests None declared.

  • Ethics approval Wakayama Medical University.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.