Background: HER2/neu overexpression on cell membranes of breast cancer cells is due to HER2/neu gene amplification and it is important to identify potential candidates for anti HER2 therapy with trastuzumab. IHC, FISH and CISH are standard FDA approved assays currently used to determine HER2 status in routine practice. The aim of this study was to determine HER2 gene amplification, using the CISH method in breast carcinoma samples which had IHC +2 reactions. Materials and
Methods: This study was conducted from 2008- 2010 using 334 consecutive breast carcinoma samples referred from local laboratories to Mehr Hospital. CISH assays were performed for all cases, and IHC tests were also done for determining efficacy and accuracy of local labs. HER2 status in local IHC tests was compared with central IHC and CISH results.
Results: Of 334 breast cancer patients, 16 were negative for HER2 IHC (0, +1), 201 cases were equivocal (+2), and 31 positive (+3). Of 334 referral cases, 88 were CISH positive (26.3%) and 246 were CISH negative (73.7%). Of 201 IHC +2 cases, HER2 gene amplification was observed in 42 cases (kappa: 0.42). A 29.9% concordance was found between local IHC and central IHC. Sensitivity and specificity of local IHC were 90% and 53.8%, respectively.
Conclusions: Low accuracy of IHC results in local labs was associated with the following factors: using former FDA-approved criteria for HER2 interpretation, utilizing non-validated kits, and lack of any quality assurance program. Therefore, following the new 2014 ASCO/CAP guideline and comprehensive quality assurance should be implemented to ensure accuracy of HER2 testing.