Abstract C72: Improving the accuracy and diagnostic power of prostate biopsy for African American patients: The Birmingham Alabama Prostate Cancer (BAPrCa) Consortium

Study Purpose: Both incidence and mortality data show that the burden of prostate cancer (PrCa) is greater in African Americans (AA) than in European Americans (EA). Socioeconomic factors contribute to this health disparity, but do not fully account for observations that AA are more likely than others to be diagnosed with more aggressive and life threatening forms of PrCa. Prostate biopsies usually establish the diagnosis of PrCa and are used to estimate the extent of the disease (based on the number and location of cores with cancer and involvement of individual cores) and its potential aggressiveness (based on Gleason scores). Health policy groups recommend that men with limited low grade prostate cancer be managed by active surveillance (AS) rather than immediate surgical or radiation treatment. However, the standard-of-care prostate biopsy is limited by sampling error and the possibility that a high grade PrCa might have been missed is a significant concern for many patients who are considering AS; this concern is heightened for AA because of their higher risk of aggressive disease. Moreover, AA are more likely to be diagnosed with high grade/high stage prostate cancer that is not treated surgically and thus not well represented in molecular studies that utilize radical prostatectomy specimens. Our research team established the Birmingham Alabama Prostate Cancer (BAPrCa) Consortium with a major focus on the molecular analysis of prostate biopsies in order to increase the clinically actionable information that can be obtained from these specimens. We use an ancestry-informed approach that is specifically designed to improve the accuracy and diagnostic power of prostate biopsy for AA patients. Experimental Procedures: The BAPrCa Consortium implemented an innovative prostate biopsy “tissue print” technology that permits collection of snap-frozen nitrocellulose blots of biopsy cores without diagnostically compromising these specimens. Tissue prints provide high quality RNA and DNA from biopsies from the full range of patients, including AAs whose cancer is too advanced at diagnosis for radical prostatectomy; this permits the molecular characterization of PrCa subtypes in men diagnosed with high volume/high grade disease who have not been adequately represented in previous molecular profiling studies. Our BAPrCa research protocols include informed consent for genetic ancestry admixture studies. Gene expression analysis of prostate biopsy tissue prints is correlated with histopathology and multiparametric prostate MRI. Results: Our data suggest that in the Birmingham area, higher prostate cancer risk in AA is associated with increasing proportion of West African (WA) ancestry, which may reflect the prevalence of population-specific genetic mutations or variations that contribute to the development of more aggressive disease. As a group, the men diagnosed with high grade PrCa showed a significantly higher level of WA ancestry than the men diagnosed with no cancer (P = 0.001). A similar pattern is observed in comparisons of AA men diagnosed with high grade cancer vs low grade PrCa. Inasmuch as our AIMs genotyping panel uses a small number of well-established AIMS markers, our observation of significantly increased risk of PrCa in AA men with high %WA AIMS ancestry may, if confirmed, have immediate potential clinical applications for improving prostate cancer screening and active surveillance. Moreover, gene expression profiles of biopsies from BAPrCa patients diagnosed with high volume/high grade PrCa revealed two subtypes of high grade PrCa with striking differences in the pathways that drive a shift in tumor fatty acid metabolism; one is a fatty acid synthase (FASN) dominant phenotype and the other a previously unrecognized fatty acid binding protein (FABP5) dominant phenotype. Our data suggest that the FABP5 dominant PrCa subtype is more common in AA and the FASN dominant subtype more common in EA. These findings may provide the basis for more effective dietary interventions and targeted therapies for AA and EA patients with high grade PrCa. Conclusions: By utilizing innovative tissue print techniques for the molecular analyses of prostate biopsies and using an ancestry informed approach in our study designs, the Birmingham Alabama Prostate Cancer (BAPrCa) Consortium has identified new and potentially actionable PrCa signatures that may improve the accuracy and diagnostic power of prostate biopsy for AA patients. Citation Format: Sandra M. Gaston, Soroush Rais-Bahrami, Rick Kittles, Kerry Dehimer, Dennis Otali, Jeffrey W. Nix, Peter N. Kolettis, George Adams, William E. Grizzle. Improving the accuracy and diagnostic power of prostate biopsy for African American patients: The Birmingham Alabama Prostate Cancer (BAPrCa) Consortium. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C72.