A universal immunohistochemistry analyzer for generalizing AI-driven assessment of immunohistochemistry across immunostains and cancer types

Abstract

Abstract Immunohistochemistry (IHC) is the common companion diagnostics in targeted therapies. However, quantifying protein expressions in IHC images present a significant challenge, due to variability in manual scoring and inherent subjective interpretation. Deep learning (DL) offers a promising approach to address these issues, though current models require extensive training for each cancer and IHC type, limiting the practical application. We developed a Universal IHC (UIHC) analyzer, a DL-based tool that quantifies protein expression across different cancers and IHC types. This multi-cohort trained model outperformed conventional single-cohort models in analyzing unseen IHC images (Kappa score 0.578 vs. up to 0.509) and demonstrated consistent performance across varying positive staining cutoff values. In a discovery application, the UIHC model assigned higher tumor proportion scores to MET amplification cases, but not MET exon 14 splicing or other non-small cell lung cancer cases. This UIHC model represents a novel role for DL that further advances quantitative analysis of IHC.