Silver-enhanced in situ hybridization as an alternative to fluorescence in situ hybridization for assaying HER2 amplifcation in clinical breast cancer

Abstract

Purpose: Valid determination of HER2 status is a prerequisite to establish an adequate treatment strategy for breast cancer patients, regardless of the disease stage. The goal of this study was to examine the feasibility of the newly developed silver-enhanced in situ hybridization (SISH) technique as an alternative to fuores-cence in situ hybridization (FISH) for HER2 assay in primary invasive breast cancer. Methods: FISH and SISH for HER2 amplifca-tion were performed using tissue microarray. Both methods were used in 257 consecutive primary breast cancers. Results: HER2 amplifcation was observed in 62 (23.1%) of a total of 257 breast cancers based on SISH. Of the 257 breast cancers measured using both methods, the results of the two methods were consistent in 248 (concordance, 96.5%; kappa=0.903). When we compared HER2 amplifcation in the primary tumor with the meta-static lymph nodes of the same patients, HER2 amplifcation was observed in nine cases (14.0%) out of 64 cases in which HER2 was not amplifed in the primary tumors. In contrast, HER2 status was completely preserved in metastatic lymph nodes showing HER2 amplifcation in the primary tumor. Conclusion: These results indicate that SISH can be a feasible alternative to FISH in the clinical setting. In node-positive breast cancer, confrmation of the HER2 status of the metastatic lymph nodes appears to be mandatory, regardless of the HER2 status of the primary tumors.