HER2 status in gastric cancer: a comparison of two novel in situ hybridization methods (IQ FISH and dual color SISH) and two immunohistochemistry methods (A0485 and HercepTest™).

In contrast to breast HER2 testing, the optimal ISH method and antibody for gastric HER2 testing are unclear. The aim of this study was to find out gastric HER2 positivity rates in our institutional data, and to compare the two novel ISH methods with A0485 antibody and HercepTest™. IHC and ISH were carried out on gastrectomy specimens of 88 patients up to the standardly advised procedure protocols, and interpretations were also carried out up to widely accepted international protocols., HER2 expression was (-) in 65, (+) in 5, (++) in 6, and (+++) in 12 cases by A0485 IHC. IHC (+) 4 cases and (++) 3 cases were (-) by HercepTest™. One IHC (-) amplified case was (++) by HercepTest™. All A0485 and HercepTest™ (+++) 12 cases were amplified by ISH. HER2 amplification was detected in 18 (20.4%) and in 15 (17.2%) cases by SISH and FISH, respectively. Of the 18 cases, 4 showed focal heterogeneous low level amplification by SISH. Focal amplification was noted in only 2 cases by FISH. The HER2 status of our gastric cancer file is 17.2% by FISH, 20.4% by SISH. The concordance between HercepTest™/A0485 IHC and ISH is perfect in (+++) cases. Equivocal results (++) with any IHC method should be clarified by one of the molecular methods (SISH and FISH). Probably up to the higher level of heterogeneity of gastric carcinomas, there is a 4.5% dilemma of cases that are negative or weakly positive by conventional IHC methods. Therefore, regarding HER2 status in gastric carcinoma, the reliability of IHC methods should be checked.