FOXA1 is a highly sensitive diagnostic marker for prostate cancer including small cell carcinoma of the prostate

Prostate cancer is one of the most common malignancies in men and a major cause of cancer-related mortality worldwide. While second-generation antiandrogens induce durable responses, they have also led to the emergence of aggressive, androgen-independent subtypes of prostate cancer, including small cell carcinoma of the prostate. The diagnosis of these subtypes remains challenging due to the frequent loss of traditional prostatic markers, and novel prostate-specific markers are needed in routine pathology practice.

Through analysis of the Cancer Genome Atlas (TCGA) database, we identified Forkhead box protein A1 (FOXA1) as a potential diagnostic marker for prostatic cancer. We compared FOXA1 and NKX3.1 expression in benign prostatic glands and prostatic adenocarcinoma; FOXA1 immunostaining demonstrated a similar nuclear staining pattern to NKX3.1 and a high sensitivity for prostatic adenocarcinoma. Notably, in small cell carcinoma of the prostate, which typically loses expression of traditional prostate markers, FOXA1 expression was detected in 8 of 10 (80%) primary cases and 12 of 21 (57%) metastatic cases in our cohort. We also evaluated FOXA1 expression across various tumour types and observed positivity in 25 of 44 (57%) breast carcinomas, 15 of 68 (22%) urothelial carcinomas and rarely in other tumour types. Among 106 neuroendocrine tumours/carcinomas from different organs, only 2 of 4 breast neuroendocrine carcinomas showed FOXA1 expression.

FOXA1 is a highly sensitive diagnostic marker for prostate cancer. It can serve as a valuable adjunct for confirming prostatic origin in diagnostically challenging cases such as prostatic small cell carcinoma.