Objective:

To evaluate the potential of FOXA1 as a biomarker for identifying aggressive forms of prostate cancer, particularly in cases where conventional diagnostic markers are lost.

Key Findings:

• FOXA1 showed high sensitivity for prostate adenocarcinoma, even when conventional markers were lost.
• FOXA1 remained detectable in many cases of small cell carcinoma of the prostate, which often loses traditional markers.
• Positive FOXA1 staining was observed in 76 of 81 primary prostate adenocarcinomas and all 11 metastatic adenocarcinomas.
• In small cell carcinoma, FOXA1 expression persisted in 80% of primary cases and 57% of metastatic cases, despite loss of conventional markers.

Interpretation:

FOXA1 may assist in identifying the tissue of origin in metastatic neuroendocrine tumors in patients with a history of prostate cancer, addressing the diagnostic challenges posed by small cell carcinoma.

Limitations:

• Further validation studies are needed to confirm FOXA1's clinical utility across diverse tumor types.
• The study does not address the potential role of FOXA1 in prognostic stratification and targeted therapy development.

Conclusion:

FOXA1 could serve as a valuable adjunct immunohistochemical marker in surgical pathology for aggressive prostate cancers, especially in the context of treatment resistance.