Abstract 4631: Enhancement of prostate cancer diagnosis through distribution analysis of a biomarker for apoptosis within subcellular fractions of prostate biopsy cores
Authors: WenKui Lan, Marc J. Horn, Win Truong, Micheal LaSalle, Joseph Ditrolio
Journal: Cancer Research (2010)

Abstract Introduction: A major problem inherent in prostate cancer (PCa) management is the lack of specificity of the PSA test. Other tests - DRE, PCA-3 plus and standard 12 core ultrasound guided biopsies (TRUS) - also do not always accurately predict a definitive diagnosis. More sensitive and specific tests are needed. Glucose-regulated protein GRP78, an apoptosis marker, is reported to be related to several human cancers. In this study, we evaluated GRP78 as a PCa biomarker using EDGE*TEST™ (E*T), a subcellular fractionation/statistical analysis technology, to determine if it can detect and differentiate PCa from BPH, and if it can predict PCa activity throughout the prostate rather than through individual targeted biopsies. Methods: Twenty four patients with elevated PSA, abnormal DRE and/or elevated PCA-3 plus genetic test had 12 core TRUS biopsies performed by a single urologist. At time of biopsy, additional random two core prostate biopsies (one per lobe) were collected for E*T. The two cores were combined, homogenized and nuclei removed. Post-nuclear supernatants were fractionated, using Edge 200 Separation System, into 4 subcellular fractions, the fractions subjected to western blot analysis using GRP78, and GRP78 distribution ratios analyzed against the number of positive PCa biopsy cores and cores negative for cancer. E*T analyses of patients’ relative distribution profiles were blinded against all clinical and pathology data. Negative Pca biopsy patients were followed up 18 months to compare E*T to traditional screening and biopsy. Preliminary Results: Results of TRUS biopsies showed 8/24 patients had PCa as diagnosed on initial biopsy. Cores per patient ranged from 2-12/12 regions positive for PCa. E*T, with 2 random cores, correlated with 7/8 (87.5%) diagnosed cancers. Of 16 patients initially tested with 0/12 core biopsies positive for PCa, 15/16 (93.8%) were correctly correlated by E*T with non-cancerous disease. Of the initial 15 patients correctly diagnosed by E*T with benign disease and not cancer, only one patient developed cancer on subsequent biopsy. After 18 months follow-up, 7/9 (88.9%) of PCa was detected by E*T based upon initial biopsy. Based on initial biopsy, E*T had a false positive of 1/16 (6.25%) with PCa not detected yet on follow up. E*T had a false negative of 1/16 (6.25%) initially for cancer. Of 16 patients having 0/12 core biopsies PCa positive, 15/16 (93.8%) remained without cancer after 18 months follow-up. E*T was consistent with 14/16 (87.5%) patients, based on initial biopsy, showing high predictive data of benign disease and not cancer. PSA, DRE and PCA-3 were all inconsistent individual or combined indicators. EDGETEST of two random biopsies correlated strongly with PCa activity by evaluating apoptosis and was consistent over 18 month follow up. EDGETEST may be a complementary predictor of PCa over benign disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4631.