Detection of glypican-1 (GPC-1) expression in urine cell sediments in prostate cancer

• Published in: PloS one Vol. 13; no. 4; p. e0196017
• Main Authors: Campbell, Douglas H, Lund, Maria E, Nocon, Aline L, Cozzi, Paul J, Frydenberg, Mark, De Souza, Paul, Schiller, Belinda, Beebe-Dimmer, Jennifer L, Ruterbusch, Julie J, Walsh, Bradley J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.04.2018; Public Library of Science (PLoS)
• Subjects: Antigens; Assaying; Biological products; Biology and Life Sciences; Biomarkers; Biopsy; Bladder; Cancer; Cancer screening; Care and treatment; Cellular biology; Confidence intervals; Diagnosis; Earth Sciences; Glycoproteins; Health aspects; Heparan sulfate; Heparan sulfate proteoglycans; Hyperplasia; Immunofluorescence; Medical diagnosis; Medical research; Medicine; Medicine and Health Sciences; Monoclonal antibodies; Oncology; Patients; Prostate cancer; Prostatic hyperplasia; Research and Analysis Methods; Sediments; Sensitivity; Surveillance; Urine; Urology; Victoria Australia; Australia; Detroit Michigan; United States > US; New South Wales Australia; Michigan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0196017

While measurement of serum prostate specific antigen (PSA) is an important screening tool for prostate cancer, new biomarkers are necessary for better discrimination between presence and absence of disease. The MIL-38 monoclonal antibody is specific for the membrane glycoprotein glypican 1 (GPC-1) and binds to prostate cancer tissue. Urine is known to be a source of cellular material. Thus, we hypothesized that detection of GPC-1 in urine cellular material may identify individuals with prostate cancer. Urine samples from patients with prostate cancer, benign prostatic hyperplasia (BPH), or normal controls were collected and cell sediments prepared. GPC-1-positive cells were detected using a MIL-38 immunofluorescence assay (IFA) and samples were classed positive or negative for GPC-1 expressing cells. Assay sensitivity and specificity, stratified by PSA, was reported. A total of 125 patient samples were analyzed (N = 41 prostate cancer; N = 37 BPH; N = 47 normal controls). The use of MIL-38 to detect GPC-1 by IFA discriminated between prostate cancer and BPH urine specimens with a sensitivity and specificity of 71% and 76%, respectively. Assay specificity increased with increasing PSA, with the highest specificity (89%) for patients with PSA ≥4 ng/ml. At lower PSA (<2 ng/ml) specificity decreased, as evidenced by a greater number of false positives in this concentration range. The odds ratio (OR) and 95% confidence intervals (CIs) for GPC-1-positive cells in patients with prostate cancer, adjusted for PSA, was greatest at the lowest serum PSA (<2 ng/ml; OR = 13.4; 95% CI: 4.0-44.7) compared with no adjustment for PSA (OR = 6.4; 95% CI: 2.8-14.9). The use of MIL-38 for detection of GPC-1 may be a useful tool for detection of prostate cancer.