Molecular Biomarker Testing in Kidney Cancer: Integrating Diagnosis, Prediction, and Emerging Renal Tumor Entities

Background

Kidney tumors comprise a biologically diverse and diagnostically challenging group of neoplasms. Many entities share overlapping morphologic features despite having distinct molecular profiles. Although histomorphology remains the cornerstone of diagnosis, molecular biomarker testing has become increasingly important for accurate classification, recognition of emerging entities, identification of hereditary cancer syndromes, and therapeutic decision-making. Focus of the Review: This narrative review provides a practical, pathology-oriented framework for molecular biomarker testing in kidney tumors. It integrates immunohistochemistry, fluorescence in situ hybridization, polymerase chain reaction-based methods, and next-generation sequencing with morphologic assessment. Particular attention is given to diagnostically relevant alterations involving VHL, TFE3, TFEB, MET, FH, ELOC, and ALK, genes encoding SDH subunits, and components of the mTOR signaling pathway, together with commonly used immunohistochemical surrogates. The prognostic and predictive roles of selected biomarkers, including their potential value in hereditary risk assessment and treatment selection, are also discussed. Practical limitations, such as limited biopsy material, intratumoral heterogeneity, and technical variability, are considered.