Abstract A47: Prostate biopsy tissue print technologies: A practical and innovative approach to overcoming racial disparities in the datasets used for prostate cancer biomarker development

Abstract

Abstract Health disparities can be unintentionally aggravated by patterns of medical practice that shape biomedical research. In prostate cancer research, radical prostatectomy specimens have been the major source of frozen tissue samples used for the molecular genetic analysis of primary prostate cancers. However, because men who are diagnosed with relatively advanced prostate cancer are more likely to be offered hormonal and/or radiation treatment, the patients who are diagnosed too late to be offered surgery are underrepresented in conventional tissue banks that depend upon radical prostatectomy specimens. As a result, the prostate cancer patients who are diagnosed with the most serious forms of this disease are significantly underrepresented in the gene expression datasets that have become central to biomarker and therapeutic target discovery. African American men are particularly impacted by this under-representation, both because they are more likely to be diagnosed with relatively advanced prostate cancer and because of a preference in many African American communities for non-surgical forms of prostate cancer treatment. Potentially, a more representative collection of samples could be obtained from newly diagnosed, untreated prostate cancers by utilizing the diagnostic prostate biopsy specimens. The prostate biopsy population includes the entire range of newly diagnosed cancers; it also includes all of the patients whose biopsies are cancer-negative. However, there are well recognized barriers to obtaining samples from diagnostic prostate biopsies for research. In most settings, each prostate biopsy core must be processed in its entirety as a formalin-fixed paraffin embedded (FFPE) specimen and the remnant FFPE biopsy tissue is often relatively limited and potentially compromised by fixation and processing. We have overcome the barriers to using routine diagnostic biopsies for molecular biomarker studies by developing a set of tissue printing technologies that allow us to obtain high quality DNA and RNA from each biopsy core without compromising pathology diagnosis. These tissue printing technologies have now been successfully applied to a range of cancer studies, including molecular analyses of metastatic lesions which are frequently available only as needle biopsies. We have formed a collaboration in which tissue print technologies are used to support a systematic comparison of molecular biomarker patterns in prostate biopsies obtained from African American and European American patients. Our data analysis plan includes an evaluation of marker associations with both self-identified ancestry and with genetic lineage as defined by ancestry informative markers. This approach has been particularly interesting in the evaluation of DNA methylation markers, where it has been demonstrated that the extent of cancer-associated hypermethylation depends in part on the DNA sequence of the marker allele. More generally, because the use of biopsy samples allows us to obtain a more representative sample of the African Americans and European American patient populations, we can improve the pre-clinical assessment of potential strengths and weaknesses of specific biomarker tests as tools for guiding patient care Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A47.