655P - Comparison of HER2 immunohistochemical staining in primary signet ring cell carcinoma; Pathway versus HercepTest

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Gastric Cancer
Pathology/Molecular Biology
Basic Scientific Principles
Basic Principles in the Management and Treatment (of cancer)
Presenter Woo Chang Gok
Citation Annals of Oncology (2014) 25 (suppl_4): iv210-iv253. 10.1093/annonc/mdu334
Authors W. Chang Gok1, H.J. Park2, M.H. Ryu3, P. Suk Ryun2, Y.S. Park4
  • 1Pathology, Asan Medical Center, 138-736 - Seoul/KR
  • 2Medical Oncology, Asan medical center, Seoul/KR
  • 3Division Of Oncology, Dept Of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul/KR
  • 4Department Of Pathology, Asan Medical Center, 138-736 - Seoul/KR



Trastuzumab has shown efficacy in gastric cancers with HER2 amplification. Immunohistochemical (IHC) staining is used for screening and in situ hybridization (ISH) is done as adjunct. One the FDA approved IHC method, PATHWAY, occasionally shows strong nuclear and/or cytoplasmic staining, which should not be considered positive. This can sometimes be misinterpreted as true membranous staining especially in signet ring cell carcinoma (SRC) because the cytoplasms of these tumor cells are marginated against the membrane. We compared the IHC staining results in SRC with other FDA approved IHC method (HercepTest) and confirmed the results with ISH.


Stage IV primary gastric SRC was retrospectively collected from 2009 to 2012. We analyzed 157 patients who had tumor tissue available for IHC and ISH. After scoring HER2 IHC (PATHWAY and HercepTest), all score 2+ and 3+ cases and those showing discrepancy between two IHC methods were confirmed with silver ISH (SISH).


Twenty-five cases (15.9%) showed discrepancy (concordance rate = 67.5%; κ = 0.275) between two IHC methods. The concordance rate of IHC 3+ and HER2 amplification by SISH was 100% in HercepTest (κ = 1.000) but 15.8% in PATHWAY (κ = 0.018). These discrepancies were caused by strong nuclear/cytoplasmic staining which was observed only in PATHWAY method (10.2%) and none of these showed HER2 amplification by SISH.


Misinterpretation of HER2 IHC can lead to unnecessary administration of trastuzumab. Since interpretation of IHC using PATHWAY method can be erred in gastric SRC, other staining method or ISH confirmation should be considered.


All authors have declared no conflicts of interest.