A Validation Study of Human Epidermal Growth Factor Receptor 2 Immunohistochemistry Digital Imaging Analysis and its Correlation with Human Epidermal Growth Factor Receptor 2 Fluorescence Hybridization Results in Breast Carcinoma.

BACKGROUND

The Visiopharm human epidermal growth factor receptor 2 (HER2) digital imaging analysis (DIA) algorithm assesses digitized HER2 immunohistochemistry (IHC) by measuring cell membrane connectivity. We aimed to validate this algorithm for clinical use by comparing with pathologists' scoring and correlating with HER2 fluorescence hybridization (FISH) results.

MATERIALS AND METHODS

The study cohort consisted of 612 consecutive invasive breast carcinoma specimens including 395 biopsies and 217 resections. HER2 IHC slides were scanned using Philips IntelliSite Scanners, and the digital images were analyzed using Visiopharm HER2-CONNECT App to obtain the connectivity values (0-1) and scores (0, 1+, 2+, and 3+). HER2 DIA scores were compared with Pathologists' manual scores, and HER2 connectivity values were correlated with FISH results.

RESULTS

The concordance between HER2 DIA scores and pathologists' scores was 87.3% (534/612). All discordant cases ( = 78) were only one-step discordant (negative to equivocal, equivocal to positive, or vice versa). Five cases (0.8%) showed discordant HER2 IHC DIA and FISH results, but all these cases had relatively low copy numbers (between 4 and 6). HER2 IHC connectivity showed significantly better correlation with copy number than ratio.

CONCLUSIONS

HER2 IHC DIA demonstrates excellent concordance with pathologists' scores and accurately discriminates between FISH positive and negative cases. HER2 IHC connectivity has better correlation with copy number than ratio, suggesting copy number may be more important in predicting HER2 protein expression, and response to anti-HER2-targeted therapy.