Effectiveness of Silver-enhanced In Situ Hybridization for Evaluating HER2 Gene Status in Invasive Breast Carcinoma: A Comparative Study

Background and Aims: HER2 gene amplification occurs in breast cancers and has implications for treatment and prognosis. Recently, a new direct evaluation technique, silver enhanced in situ hybridization (SISH) was developed for evaluating HER2 gene status. This study was performed to evaluate the SISH technique for clinical use by comparing it to that of fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Methods: We studied 543 cases of excised breast specimens diagnosed as invasive ductal carcinoma by IHC, FISH, and SISH using a tissue microarray. IHC, FISH, and SISH results were interpreted according to the American Society of Clinical Oncology/College of American Pathologists guidelines. A total of seven English studies that reported the concordance rates of SISH and BDISH compared to FISH published before July 2011 were retrieved. Results: The consensus concordance rate between SISH and FISH was 96.69% (kappa value = 0.9175). The pooled sensitivity was 0.94 [95% confidence interval (CI) = 0.91-0.97], and the pooled specificity was 0.98 (95% CI = 0.96-099) in a meta-analysis of the retrieved studies and this study. Area under the receiver operating characteristics curve was 0.9906. Conclusions: SISH technique is an effective modality and is comparable with FISH for evaluating HER2 gene amplification in patients with breast carcinoma.