Ability of PSA-positive circulating macrophages to detect prostate cancer

Prostate-specific antigen (PSA) is a widely used serum marker for prostate cancer, but has a poor specificity for early detection at levels below 10 ng/ml, because it can also result from benign conditions. Our aim was to determine the frequencies of circulating PSA+ macrophages in a blinded study and to examine the suitability of this new method for differentiating between benign and malignant prostate disease.

Between October 2002 and February 2003, 126 patients undergoing transrectal biopsy were enrolled in this study. Peripheral blood macrophages were stained for intracellular content of PSA in all patients. Ten patients' peripheral blood mononulear cells (PBMCs) were also supplementarily stained for cytokeratin (CK) and epithelial membrane antigen (EMA). Macrophages were analysed by flow cytometry. Patients were grouped according to their biopsy histology and bone scan results.

Based on histological data, patients were classified as having no evidence of malignancy (NEM) (n = 59), prostatitis (n = 20), or localised prostate cancer (n = 37). Significantly higher levels of circulating PSA+ macrophages were found in prostate cancer compared to benign conditions. Calculating a 2% cut-off level enabled the detection of localised prostate cancer with 89% sensitivity and 80% specificity. In a subset of patients (65%) with a serum PSA below 4 ng/ml and confirmed prostate cancer, the percentage of PSA+ macrophages was significantly higher compared to NEM and prostatitis. Macrophages of ten patients tested with prostate cancer contained significantly higher amounts of PSA, EMA, and CK compared to ten with NEM.

Intracellular PSA in combination with CK and EMA can be found in permeabilized blood macrophages, indicating phagocytosis of complete cancer cells. This study further suggests, that this new method might be suitable for differentiating between prostate cancer and benign conditions especially in patients with low serum PSA.