Translational milestones in urologic pathology: integrating molecular diagnostics across cancer types

In its first decade, The Journal of Pathology: Clinical Research has become a leading source of translational studies advancing molecular diagnostics in cancer, particularly in urologic pathology. This commentary highlights recent contributions that collectively place precision oncology at the forefront of pathology research. One review examines cancer stem cells in renal cell carcinoma, emphasizing the complexity of cellular plasticity and the tumor microenvironment in driving resistance and recurrence. In prostate cancer, epithelial-to-mesenchymal transition (EMT) regulators, including Twist, Slug, and Snail, are identified as synergistic markers of poor prognosis, linked to hypoxia and invasiveness. Another review details the integration of homologous recombination repair gene testing into clinical workflows, supporting targeted treatment strategies with poly (ADP-ribose) polymerase inhibitors. In pediatric oncology, TP53 alterations in Wilms tumor are shown to occur beyond anaplastic cases, expanding their prognostic significance. Advances in molecular subtyping are also demonstrated in bladder cancer, where transcriptomic profiling could enable tailored neoadjuvant therapy. In clear cell renal cell carcinoma, re-evaluation of a prognostic model revealed that while necrosis or sarcomatoid differentiation correlated with poor outcomes, only DNA methylation markers improved prognostic accuracy, underscoring their utility for biopsy-based risk stratification. Finally, digital spatial profiling of sarcomatoid urothelial carcinoma reveals an immunosuppressive microenvironment with CD163-positive cells, implicating them in EMT and aggressive phenotype. Together, these studies highlight the transformative role of integrated molecular diagnostics in guiding individualized therapies and improving outcomes in urologic cancers.