The role of tissue microarrays in prostate cancer biomarker discovery

Hospital Pathology Associates, Abbott Northwestern Hospital, University of Minnesota, Minneapolis, MN 55407, USA.
Advances in Anatomic Pathology (Impact Factor: 3.23). 12/2007; 14(6):408-18. DOI: 10.1097/PAP.0b013e318155709a
Source: PubMed


Tissue microarrays (TMAs) offer the potential to rapidly translate genomics and basic science research findings to practical clinical application. This is particularly true in the field of cancer biomarker research, where TMAs can be used for candidate biomarker validation and association with patient clinical, pathologic, and outcomes parameters. In this review, we examine the effect of TMA use on prostate cancer biomarker research, focusing on the types of TMAs that have been used, and the biomarkers that have been examined. The results demonstrate that TMAs have been very effective in screening candidate biomarkers for subsequent, extended evaluation in large patient populations. In addition, the use of TMAs in multiple biomarker series allows for the statistical analysis of sets of biomarkers as diagnostic or prognostic tests. The processes used here can be applied to any tumor type to improve patient diagnosis, prognosis, and treatment response prediction.

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    • "[6]–[12]. Differential display technology has been used successfully to identify changes in the level of gene expression associated with the transition from normal to tumour which include genes involved in lipid signalling and metabolism; fatty acid synthesis; cell cycle regulation; cell adhesion and stromal regulation; angiogenesis; ion channel regulation, and signal transduction [13], [14]. Using differential display Bussemakers et al [15] identified a cDNA, subsequently named prostate cancer antigen 3 (PCA3/DD3), that was upregulated in 53 of 56 prostate cancers when compared with non-malignant prostate tissue. "
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    ABSTRACT: The prostate cancer antigen 3 (PCA3/DD3) gene is a highly specific biomarker upregulated in prostate cancer (PCa). In order to understand the importance of PCA3 in PCa we investigated the organization and evolution of the PCA3 gene locus. We have employed cDNA synthesis, RTPCR and DNA sequencing to identify 4 new transcription start sites, 4 polyadenylation sites and 2 new differentially spliced exons in an extended form of PCA3. Primers designed from these novel PCA3 exons greatly improve RT-PCR based discrimination between PCa, PCa metastases and BPH specimens. Comparative genomic analyses demonstrated that PCA3 has only recently evolved in an anti-sense orientation within a second gene, BMCC1/PRUNE2. BMCC1 has been shown previously to interact with RhoA and RhoC, determinants of cellular transformation and metastasis, respectively. Using RT-PCR we demonstrated that the longer BMCC1-1 isoform - like PCA3 - is upregulated in PCa tissues and metastases and in PCa cell lines. Furthermore PCA3 and BMCC1-1 levels are responsive to dihydrotestosterone treatment. Upregulation of two new PCA3 isoforms in PCa tissues improves discrimination between PCa and BPH. The functional relevance of this specificity is now of particular interest given PCA3's overlapping association with a second gene BMCC1, a regulator of Rho signalling. Upregulation of PCA3 and BMCC1 in PCa has potential for improved diagnosis.
    PLoS ONE 02/2009; 4(3):e4995. DOI:10.1371/journal.pone.0004995 · 3.23 Impact Factor
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    • "Maraldo et al. quantified AMACR from urine without sample preparation using a macrocantilever-based technique. Thus, biomarkers associated with the presence of prostate cancer have been extensively studied using electrophoresis, protein expression, tissue microarrays , macrocantilevers, tandem mass spectrometry (LC MS/MS), matrix-assisted laser desorption ionization (MALDI) and surface enhanced laser desorption ionization (SELDI)-mass spectrometry (MS) [10] [11] [12] [13], but these potential biomarkers still need to undergo validation before acceptance in the clinical laboratory. Changes in glycosylation have been implicated in many diseases including cancer [14] [15] [16] [17] [18]. "
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    ABSTRACT: Prostate cancer is a leading cause of cancer death among men. Currently available screening test measures prostate-specific antigen (PSA) to detect prostate cancer. However, this test produces false positive values that often lead to negative biopsies. Therefore, a more reliable diagnostic tool is needed. Glycans in serum are of particular interest as around half of all proteins are glycosylated. In this study, N-linked glycans were enzymatically released by PNGase F from prostate epithelial cell lines (pRNS) expressing wild type or mutant androgen receptors and a small set of human serum samples. Released glycans were purified and partitioned into neutral and acidic components by solid phase extraction (SPE) using graphitized carbon cartridges. The SPE fractions were analyzed by matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry (MALDI FT-ICR MS). Significant changes in some high-mannose and fucosylated biantennary complex N-linked glycans were observed in the serum of prostate cancer patients.
    Disease markers 02/2008; 25(4-5):243-58. DOI:10.1155/2008/515318 · 1.56 Impact Factor
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    ABSTRACT: This review is intended to provide an overview of 'best practices' pertaining to prostate biobanking. It addresses issues related to collection and appropriate annotation of prostate samples, ethics and administrative aspects of biorepository functioning. Paraffin tissue microarrays have emerged as a significant mechanism for high throughput evaluation of markers of interest. In addition, modification of guidelines and definitions of 'human research' have served to provide mechanisms for expediting biological specimen disbursement. A well developed biobank is a critical prerequisite for high-quality research. This review provides an outline of certain critical elements that would need careful attention as a prostate cancer biobank is developed.
    Current Opinion in Urology 06/2008; 18(3):309-14. DOI:10.1097/MOU.0b013e3282fb7cbe · 2.33 Impact Factor
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