Molecular Biomarker Testing in Kidney Cancer: Integrating Diagnosis, Prediction, and Emerging Renal Tumor Entities
9 affiliations
- 1Department of Pathology, School of Medicine, Kocaeli University, Kocaeli 41001, Turkey
- 2Department of Pathology, Gulhane Research and Training Hospital, Ankara 06010, Turkey
- 3Department of Urology, School of Medicine, Kocaeli University, Kocaeli 41001, Turkey
- 4Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA
- 5Section of Pathology, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy
- 6Department of Pathology, Pederzoli Hospital, 37019 Peschiera, Italy
- 7Department of Pathology, School of Medicine, Atlas University, Istanbul 34408, Turkey
- 8Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02115, USA
- 9Department of Pathology and Laboratory Medicine, Department of Surgery (Urology), Brown University Warren Alpert Medical School, the Legorreta Cancer Center at Brown University, and Brown University Health, Providence, RI 02912, USA
Abstract
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. Conclusions: Molecular biomarker testing is reshaping kidney tumor pathology by supporting an integrated diagnostic approach that complements, rather than replaces, careful morphologic evaluation. Its appropriate use can improve diagnostic accuracy, refine clinical stratification, and facilitate the recognition of emerging renal tumor entities with hereditary or therapeutic relevance. Future developments are expected to include methylation profiling, transcriptomic classifiers, liquid biopsy platforms, and artificial intelligence-assisted interpretation.
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BibTeX
@article{bayrak2026molecular,
title = {{Molecular Biomarker Testing in Kidney Cancer: Integrating Diagnosis, Prediction, and Emerging Renal Tumor Entities}},
author = {Busra Yaprak Bayrak and Elif Ozsagir and Nazif Alperen Yıldırım and Kerem Teke and Michael Cheng and Anna Caliò and Guido Martignoni and Mahmut Akgul and Liang Cheng},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18203341},
url = {https://www.mdpi.com/2072-6694/18/20/3341},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Molecular Biomarker Testing in Kidney Cancer: Integrating Diagnosis, Prediction, and Emerging Renal Tumor Entities
AU - Busra Yaprak Bayrak
AU - Elif Ozsagir
AU - Nazif Alperen Yıldırım
AU - Kerem Teke
AU - Michael Cheng
AU - Anna Caliò
AU - Guido Martignoni
AU - Mahmut Akgul
AU - Liang Cheng
PY - 2026
DA - 2026/10/01
JO - Cancers
DO - 10.3390/cancers18203341
UR - https://www.mdpi.com/2072-6694/18/20/3341
AB - 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. Conclusions: Molecular biomarker testing is reshaping kidney tumor pathology by supporting an integrated diagnostic approach that complements, rather than replaces, careful morphologic evaluation. Its appropriate use can improve diagnostic accuracy, refine clinical stratification, and facilitate the recognition of emerging renal tumor entities with hereditary or therapeutic relevance. Future developments are expected to include methylation profiling, transcriptomic classifiers, liquid biopsy platforms, and artificial intelligence-assisted interpretation.
SN - 2072-6694
ER -