Validation of Dual-Color Dual In Situ Hybridization for HER2/neu Gene in Breast Cancer

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作   者：

Desai, Sangeeta B.;  Rathi, Aditi;  Sahay, Ayushi;  Shet, Tanuja M.;  Patil, Asawari; 

关键词：

AMPLIFICATION;  RECOMMENDATIONS;  ISH DISH;  FISH;  AMERICAN-SOCIETY; 

期刊名称：

Archives of pathology & laboratory medicine

i s s n：

0003-9985

年卷期：

2024 年 148 卷 4 期

页   码：

453-460

页   码：

摘   要：

center dot Context.-Human epidermal growth factor (HER2/neu) gene amplification, a poor prognostic factor in invasive breast cancer, has shown substantial utility as a predictive marker, with significantly improved survival following antiHER2 therapies like trastuzumab. Dual-color dual in situ hybridization (D-DISH), a recently introduced fully automated assay for HER2/neu evaluation on light microscopy, has several advantages over fluorescence in situ hybridization (FISH). Objective.-To standardize and validate the D-DISH assay using FISH as the gold standard and assess interobserver reproducibility in interpreting the D-DISH assay. Design.-D-DISH was performed using the latest HER2 Dual ISH DNA Probe Cocktail assay (Ventana Medical Systems Inc, Tucson, Arizona) in 148 cases of invasive breast cancer. The same block was used for performing immunohistochemistry by Ventana PATHWAY anti-HER2/ neu (4B5) antibody and FISH assay by ZytoLight SPEC ERBB2/CEN17 Dual Color Probe. D-DISH was separately interpreted by 4 pathologists blinded to FISH results. Results.-Concordance of 98.65% and a Cohen kappa value of 0.97 were observed between FISH and D-DISH. Intraclass correlation coefficient (0.93-0.97) and kappa values (0.98-1.0) for interobserver reproducibility showed almost perfect agreement by D-DISH. Interobserver reproducibility was also evaluated for genomic heterogeneity, HER2 group categorization, and polysomy (kappa values 0.42-0.74, 0.89-0.93, and 0.98-1.0, respectively). Conclusions.-We successfully validated the latest version of D-DISH assay as a substitute for FISH in predicting HER2 gene status with significant interobserver reproducibility, concluding that this D-DISH assay may be introduced in routine diagnostic services as a reflex test to ascertain HER2 gene status. (Arch Pathol Lab Med. 2024;148:453-460; doi: 10.5858/ arpa.