Histopathological and Immunohistochemical Evaluation of FOXA1 as a Robust Diagnostic Marker in Prostate Cancer

Background: Prostate cancer is a common cancer in Iraqi men, especially advanced and aggressive forms, that have become more frequent in recent years. Next-generation antiandrogen drugs have contributed to clinical success, but they also have been linked to the development of aggressive androgen-independent forms of cancer, such as small cell carcinoma of the prostate. It is still a significant pathological challenge to make these diagnoses as the conventional prostatic markers are often lost. Hence, the need to identify sensitive and specific biomarkers in routine pathological practice. The purpose of this study was to assess the histopathological and immunohistochemical significance of FOXA1 expression in conventional prostate adenocarcinoma and prostatic small cell carcinoma (PSCC) in Iraqi patients.
Methods: In this retrospective multicenter study, we collected a sample of 132 formalin-fixed paraffin-embedded tissue samples from Iraqi pathology laboratories from 2021 to 2025. This cohort included 92 prostatic adenocarcinoma cases, 18 prostatic small cell carcinoma cases and 22 benign prostatic tissue samples as controls. Immunohistochemical staining was performed for both FOXA1 and NKX3.1 and the staining pattern compared between the studied groups. Selected non-prostatic tumours were analyzed also for diagnostic specificity.
Results: A total of 132 formalin-fixed paraffin-embedded (FFPE) tissue samples were obtained from Iraqi pathological centres during 2021-2025, and included in this retrospective multicenter study. There were 92 cases of prostatic adenocarcinoma, 18 cases of prostatic small cell carcinoma and 22 samples of benign prostatic tissue as controls. The expression of FOXA1 and NKX3.1 were determined using immunohistochemistry, and the expression pattern was compared among the studied groups. Further comparative study was carried out on selected non-prostatic tumors as a measure of diagnostic specificity.
Conclusions: FOXA1 is a highly sensitive immunohistochemical marker in prostate cancer, and a marker of significant diagnostic value, especially in poorly differentiated prostate cancer and prostatic small cell carcinoma, which often do not express conventional prostate markers. FOXA1 is a useful complimentary marker in the routine pathology setting to establish a diagnosis of prostatic origin when confronted with a challenging case.