BRCA Testing in Prostate Cancer: A Histopathologist's Perspective

Area of Science:

• Oncology
• Pathology
• Genetics

Background:

• BRCA1/2 alterations are key biomarkers in prostate cancer (PC), impacting prognosis and response to PARP inhibitors.
• Molecular testing for BRCA alterations is expanding, increasing the need for reliable testing methods.

Purpose of the Study:

• To provide a histopathologist-focused review of BRCA testing in PC.
• To highlight pre-analytical, technical, and morphological factors affecting BRCA testing accuracy.

Main Methods:

• Narrative review of literature on BRCA testing in prostate cancer.
• Emphasis on tissue selection, specimen processing, nucleic acid preservation, and morphology.

Main Results:

• Somatic BRCA testing success depends on fixation, storage, tumor cellularity (≥10-20%), specimen type, and DNA quality.
• Bone metastasis samples need special care due to decalcification impacting nucleic acid integrity.
• BRCA-associated PCs often show higher grade/stage; intraductal carcinoma and cribriform architecture's role as surrogate markers is uncertain.

Conclusions:

• Histopathologists are central to optimizing BRCA testing through specimen selection and handling.
• Multidisciplinary collaboration is essential for supporting precision medicine in prostate cancer.
• Ensuring quality and reliability of somatic BRCA testing is vital for patient care.