86 Quick summary: Researchers have identified the FOXA1 protein as a highly sensitive diagnostic marker capable of detecting aggressive and metastatic small cell carcinoma of the prostate that often evades traditional screening methods. By maintaining expression in up to 80% of primary tumours that have lost standard conventional markers, this biomarker provides pathologists with a vital tool to accurately determine tumour origins and guide critical therapeutic decisions. This discovery has significant implications for oncology and clinical healthcare practice, offering a reliable pathway to improve patient care and survival outcomes for individuals battling treatment resistant forms of the disease. The FOXA1 protein is a potentially highly sensitive diagnostic marker for small cell carcinoma of the prostate and possibly other aggressive prostate cancer subtypes that are difficult to diagnose due to a loss of traditional prostate markers, according to researchers at The University of Texas MD Anderson Cancer Center. The study, published in Histopathology, was led by Jianping Zhao, MD, assistant professor of Anatomic Pathology. “The detectable expression of FOXA1 in most small cell carcinomas of the prostate makes it a potentially viable option for diagnosing aggressive subtypes that lose conventional markers,” Zhao said. “While further study is needed to understand the specific molecular mechanisms, we are encouraged by these results, which could help pathologists make prognostic and therapeutic decisions to improve patient care.” Standard treatment for prostate cancer includes androgen deprivation therapy, but some aggressive forms of prostate cancer develop resistance independently from androgens, leading to a poorer prognosis for these patients. In particular, small cell carcinoma of the prostate is a common, aggressive form that usually is hard to diagnose because it often loses expression of standard markers, such as NKX3.1. This makes it difficult to determine whether a metastatic tumour is the result of progression from a known tumour in the prostate or a new primary tumour from a different site. To find a novel marker for prostate cancer, the researchers used The Cancer Genome Atlas database and identified FOXA1 as a potential candidate. They then studied FOXA1 expression in tissue samples from primary and metastatic prostate cancer as well as other cancer types. FOXA1 expression was notably higher in prostate cancer and showed expression levels similar to NKX3.1. Interestingly, they detected FOXA1 expression in 80% of primary and 57% of metastatic small cell carcinomas of the prostate, meaning it was still expressed in a significant proportion of tumours that commonly lost NKX3.1 expression, making it a valuable addition to aid in diagnosis. Further evaluation is needed to understand FOXA1 expression in other aggressive subtypes of prostate cancer and comprehend its molecular mechanisms. Prospective clinical studies will also be needed to validate the use of this biomarker.