This systematic review has the purpose to characterize the accuracy of chromogenic in situ hybridization (CISH) and silver in situ hybridization (SISH), in comparison to fluorescence in situ hybridization (FISH) in the identification of human epidermal growth factor receptor-2 (HER2) overexpression and to inform decisions about test selection.
Materials and Methods:
We searched MEDLINE and EMBASE databases using these eligibility criteria: studies evaluating invasive breast cancer samples which examined agreement between CISH or SISH, and FISH, and reported sensitivity, specificity, or concordance. We performed a bivariate meta-analysis of sensitivity and specificity using a generalized linear mixed model. We used likelihood ratio tests from meta-regression to compare accuracy between HER2 tests.
The search identified 4475 articles, of which 32 were included. The summary estimates for sensitivity and specificity were 0.91 [95% confidence interval (CI), 0.85-0.95], and 0.97 (95% CI, 0.93-0.99) for SISH; 0.97 (95% CI, 0.83-1.00) and 0.99 (95% CI, 0.96-1.00) for single-probe CISH; and, 0.98 (95% CI, 0.92-0.99) and 0.98 (95% CI, 0.91-0.99) for dual-probe CISH. Significantly higher sensitivity was reported for dual-CISH than SISH (χ2: 5.36; P=0.02) when compared with the reference test FISH.
The agreement between new bright field tests (SISH and CISH) and FISH is high (≥92%). Indirect comparison of HER2 tests indicated that overall CISH performance exceeds that of SISH. The pooled estimates from this meta-analysis summarize the current published literature and, in addition to other factors such as costs differentials, can help inform future HER2 test selection decisions.