Prostate cancer is the most frequently diagnosed male visceral cancer and the second leading cause of cancer death in the United States. Standard tests such as prostate-specific antigen (PSA) measurement have poor specificity (33%) resulting in a high number of false positive reports. Consequently there is a need for new biomarkers to address this problem. The MIL-38 antibody was first described nearly thirty years ago, however, until now, the identification of the target antigen remained elusive. By a series of molecular techniques and mass spectrometry, the MIL-38 antigen was identified to be the highly glycosylated proteoglycan Glypican-1 (GPC-1). This protein is present in two forms; a membrane bound core protein of 55-60 kDa and secreted soluble forms of 40 kDa and 52 kDa. GPC-1 identification was confirmed by immuno-precipitation, western blots and ELISA. An ELISA platform is currently being developed to assess the levels of GPC-1 in normal, benign prostatic hyperplasia (BPH) and prostate cancer patients to determine whether secreted GPC-1 may represent a clinically relevant biomarker for prostate cancer diagnosis.

indeterminate PSA results who would be candidates for initial biopsy. The assay should result in a 27% reduction of prostate needle biopsies while missing only 5% of higher grade >/¼ 4+3 cancers.

e588 Background: Biomarkers that can assist clinicians and patients to proceed when PSA and /or DRE are equivocal. Such biomarkers should establish both sensitivity and specificity for prostate cancer detection in order to improve go-forward decisions to perform prostate biopsy. Following the successful use of a three-protein marker panel to increase the specificity of prostate cancer detection1 we have now used the same technology to examine whether an MIA assay can assist in differentiating aggressive from non-aggressive cancer in prostate cancer patients. Methods: Samples from patients with either aggressive prostate cancer or non- aggressive prostate cancer were obtained from two sources. The cohort criteria comprised of serum samples where blood was drawn from patients with adenocarcinoma and a PSA greater than or equal to 2ng/mL. All men were Caucasian with the exception of 3 who were African American. Non-aggressive prostate cancer was defined as having a Gleason score of 6 (n = 35) and aggressive prostate cancer was characterized as Gleason score 7 and above (n = 69). Biomarker levels were determined using a plate based ELISA for GPC-12 and a bead-based MIA assay for the other markers. Results: By using biostatistical analysis (Simplicity Bio, Switzerland) two models were identified that were able to differentiate between aggressive and non-aggressive prostate cancer. One consisted of a combination of 5 analytes and the other used 6 analytes. Model 1 containing PSA and GPC-1 plus 4 analytes produced a combined sensitivity of 81% and specificity of 78% (AUC 0.81). The second model comprising of GPC-1 with an additional 4 analytes achieved a sensitivity of 72% with a specificity of 76% (AUC 0.76). Both models had a p value of less than 0.05. By itself PSA was a poor predictor of prostate cancer with a sensitivity of 58% and specificity of 43% (AUC 0.55). Conclusions: The analytes identified by the two statistical models demonstrate potential utility for using the combined markers as a new means of differentiating aggressive prostate cancer from non-aggressive cancer. An additional study to further validate these models is currently being constructed.