BRCA Testing in Prostate Cancer: A Histopathologist’s Perspective

BRCA1/2 alterations have emerged as clinically relevant biomarkers in prostate cancer because of their prognostic significance and predictive value for response to poly(ADP-ribose) polymerase inhibitors. As indications for molecular testing expand, histopathologists play a pivotal role in ensuring the quality and reliability of somatic BRCA testing. This narrative review provides a histopathologist-oriented overview of the principal pre-analytical, technical, and morphological issues influencing BRCA testing in PC, with emphasis on tissue selection, specimen processing, nucleic acid preservation, and genotype–phenotype correlations. The success of somatic BRCA testing depends on several pre-analytical variables, including fixation, storage time, tumor cellularity (generally ≥10–20% neoplastic cells for reliable NGS analysis), specimen type, and DNA quality. Bone metastasis specimens require special attention because decalcification procedures may compromise nucleic acid integrity and molecular testing performance. From a morphological perspective, BRCA-associated PCs, especially those harboring BRCA2 alterations, are characterized by adverse clinicopathological features, including a higher grade and stage at diagnosis. Although intraductal carcinoma of the prostate and cribriform architecture are associated with genomic instability and poor prognosis, their value as surrogate markers of BRCA1/2 alterations remains uncertain. Histopathologists play a central role in optimizing BRCA testing through appropriate specimen selection, tissue handling, and multidisciplinary collaboration, thereby supporting precision medicine in prostate cancer.