Immunohistochemistry (IHC) Versus Genomic Profiling in Cancer: Roles in Precision Medicine

Precision oncology increasingly depends on accurate biomarker assessment to guide targeted therapies. Immunohistochemistry (IHC) has long been central to routine pathology due to its accessibility and diagnostic utility; however, the expanding role of molecularly driven treatments has highlighted limitations in protein-based testing. Genomic profiling, using next-generation sequencing (NGS), enables direct detection of genetic alterations that may not be reflected at the protein level. This review explored how IHC and molecular diagnostic approaches contribute to tumour diagnostic accuracy and therapeutic management across solid tumours. The review process framework followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement. Literature retrieved from PubMed, Scopus, and Web of Science yielded 15 published studies comparing IHC and genomic profiling methods in precision oncology. Genomic profiling consistently identified clinically actionable alterations that were missed or misclassified by IHC, including gene fusions, exon-skipping events, copy-number alterations, and pathogenic mutations lacking reliable protein-level surrogates. High discordance was observed for anaplastic lymphoma kinase (ALK), proto-oncogene 1, receptor tyrosine kinase (ROS1), mesenchymal-epithelial transition gene exon 14 skipping alteration (MET exon 14), human epidermal growth factor receptor 2 (HER2), mismatch repair status, and phosphatase and tensin homolog (PTEN). Across multiple tumour types, genomic testing refined molecular classification and expanded eligibility for targeted and immunotherapies beyond IHC-based assessment. The evidence reviewed indicates that genomic technologies expand tumour characterisation beyond conventional protein-based biomarkers by detecting mutations, copy-number changes, gene fusions, and other actionable molecular events. While IHC remains valuable for initial screening, integration of genomic testing is essential for accurate biomarker assessment and optimal treatment selection in modern precision oncology.