[OA-09] Assessment of different cut-offs of equivocal HER2 IHC in breast cancer for HER2 ISH to reach appropriate sensitivity, AUC and reduction of ISH assay

Chayanan Puriwat¹, Natthawadee Laokolrat¹, Panitta Sitthinamsuwan¹, Malee Warnnissorn¹, Naree Warnnissorn² and Norasate Samarnthai¹

1. Department of Pathology, Facolty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
2. Department of Pathology and Forensic Medicine, Facolty of Medicine, Thammasat University, Pathumthani, Thailand

The equivocal range of HER2 immunohistochemistry (IHC) is complete weak to moderate staining > 10% of breast cancer cells. This range has increased the numbers of HER2 in situ hybridisation (ISH) testing compared to the previous recommendations. The aim of this study was to assess different cut-offs of equivocal HER2 IHC to reach > 95% sensitivity, improved area under the ROC curve (AUC) and > 15% case reduction of ISH testing. We retrospectively recruited consecutive cases of equivocal IHC from Siriraj Hospital, diagnosed from Joly 2018 to June 2020. Breast pathologist reviewed the HER2 IHC staining intensity level and percentage. Statistical analysis compared IHC (index test) to dual-colour ISH (DISH) (reference standard). The cohort of 306 equivocal HER2 IHC cases were 56 DISH-positive and 250 DISH-negative. Cut-off at > 10% had 100% sensitivity, AUC of 0.5020 and DISH testing reduction 0%. Cut-offs with > 95% sensitivity were at > 20%, > 30%, > 40% and > 50%. Those with significantly improved AUC were >30%, >40% and >50%. Case reduction > 15% was at cut-offs > 40% and > 50%. In conclusion, weak to moderate > 40% or > 50% HER2 IHC coold be a new cut-off for HER2 DISH testing.

Keywords: breast cancer; dual-colour in situ hybridisation; HER2; immunohistochemistry; percentage cut-off