BACKGROUND Because of its role in cell motility and growth regulation, gelsolin, an actin-binding protein, has been considered a tumor suppressor and a potential prognostic marker in some neoplasias, such as breast and bladder cancer. Little is known about its immunoexpression in prostatic adenocarcinoma (PCA). METHODS Formalin-fixed, paraffin-embedded tissues of 72 prostatectomy specimens with adenocarcinoma and 8 nonneoplastic prostates from autopsies were stained with a gelsolin monoclonal antibody using the Avidin-biotin-peroxidase complex (ABC) method after microwave antigen retrieval. Immunoreactivity was evaluated in PCA, prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH), and nonproliferative glandular tissue and stroma. The results were statistically analyzed. RESULTS Consistent gelsolin immunoreactivity was seen in prostatic stromal cells, smooth muscle, endothelia, and nerves. Variable gelsolin expression was seen in 20-100% (average (A) = 65.5%) of glandular cells in nonproliferative tissue (N = 75); 0-50% (A = 9.7%) in BPH (N = 59); 0-80% (A = 8.9%) in PIN (N = 61); and 0-90% (A = 9.3%) in PCA (N = 71). The level of gelsolin expression in nonproliferative prostatic tissue was similar between prostates with PCA (A = 63.4%) and nonneoplastic prostates (A = 67.5%). The level of gelsolin expression did not correlate with age, tumor size, Gleason score, or stage. CONCLUSIONS Gelsolin is decreased in PCA, PIN, and BPH in comparison to nonproliferative tissue. The role of this downregulation in the development of PCA is not clear. The similar reduction seen in PIN and BPH suggests that this event takes place indiscriminately in hyperplasia and early tumorigenesis in the prostate, which might limit its prognostic significance in PCA.