Abstract
Hepatocellular carcinoma (HCC) remains a global health challenge due to molecular heterogeneity and frequent delayed diagnosis. This comprehensive review synthesizes recent immunohistochemistry (IHC) advancements for HCC diagnosis, prognostication, and therapeutic prediction. We systematically evaluate conventional markers, such as hepatocyte paraffin 1 (HepPar1), arginase-1 (Arg-1), and glypican-3 (GPC3), as well as emerging biomarkers, detailing their diagnostic sensitivities and specificities in HCC with varied tumor differentiation. Prognostic immunostaining markers, such as Ki-67 proliferation index and vascular endothelial growth factor (VEGF) overexpression, correlate with reduced 5-year survival, while novel immune checkpoint IHC markers (PD-L1 and CTLA-4) predict response to immunotherapy, particularly in advanced HCC. This work provides evidence-based recommendations for optimizing IHC utilization in clinical practice while identifying knowledge gaps in biomarker validation and standardization.