Annals of Surgical Oncology

, Volume 20, Supplement 3, pp 477–484 | Cite as

A Large Cohort of Consecutive Patients Confirmed Frequent HER2 Positivity in Gastric Carcinomas with Advanced Stages

  • Junhun Cho
  • Jiyun Jeong
  • Jiyoun Sung
  • Chang Ohk Sung
  • Kyoung-Mee Kim
  • Cheol Keun Park
  • Min Gew Choi
  • Tae Sung Sohn
  • Jae Moon Bae
  • Sung Kim
Translational Research and Biomarkers

Abstract

Background

Trastuzumab in association with systemic cytotoxic chemotherapy is the standard of care for patients with advanced HER2-positive gastric carcinoma (GC). However, HER2 as a prognostic factor in GC remains controversial.

Methods

HER2 overexpression and amplification was evaluated by immunohistochemistry (IHC) and silver in situ hybridization (SISH) in 2,798 GCs obtained from 2,727 gastrectomy and 71 open/laparoscopic biopsy specimens from patients with peritoneal seeding. Regional heterogeneity was defined as the proportion of tumor cells showing membranous staining in 10–70 % of tumor cells. Genetic heterogeneity was determined by the existence of HER2/CEP17 ratio higher than 2.0 in >5 to <50 % of tumor cells.

Results

In IHC, 184 cases (6.6 %) were 3+ and 44 cases (1.6 %) were 2+. Of 44 HER2 2+ cases, SISH showed HER2 gene amplification in 21 cases (47.7 %), chromosome 17 polysomy in six cases (13.6 %), and genetic heterogeneity in five cases (11.4 %). HER2 positivity found in 7.3 % of GCs was significantly associated with older age, male gender, intestinal histology, upper third in location, higher lymph node stage (p < .002), and advanced AJCC stage (p = .033). Regional heterogeneity of HER2 was closely associated with 2+ (70.5 vs 42.9 % in 3+, p = .001) and diffuse or mixed histologic type (p = .005).

Conclusions

Regional heterogeneity of HER2 expression was closely associated with weak HER2 overexpression (2+) and with diffuse or mixed histology. Polysomy of chromosome 17 would be an important cause of HER2 2+ in IHC. Frequent HER2 positivity observed in GCs with advanced stages suggests that HER2 may be involved in tumor progression and poor prognosis.

Keywords

Gastric Cancer HER2 Expression HER2 Overexpression HER2 Gene Regional Heterogeneity 

Notes

Acknowledgment

This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health & Welfare Affairs, Republic of Korea (A092255) and a Samsung Biomedical Research Institute grant (No. SBRI-CB11031).

Supplementary material

10434_2012_2818_MOESM1_ESM.docx (34 kb)
Supplementary material 1 (DOCX 33 kb)

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Copyright information

© Society of Surgical Oncology 2012

Authors and Affiliations

  • Junhun Cho
    • 1
  • Jiyun Jeong
    • 1
  • Jiyoun Sung
    • 1
  • Chang Ohk Sung
    • 1
  • Kyoung-Mee Kim
    • 1
  • Cheol Keun Park
    • 1
  • Min Gew Choi
    • 2
  • Tae Sung Sohn
    • 2
  • Jae Moon Bae
    • 2
  • Sung Kim
    • 2
  1. 1.Department of Pathology, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea
  2. 2.Department of Surgery, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth of Korea

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