HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

Review

Post-genomic applications of tissue microarrays: basic research, prognostic oncology, clinical genomics and drug discovery

A. Mobasheri1, R. Airley2, C.S. Foster3, G. Schulze-Tanzil4 and M. Shakibaei4

1Molecular Pathogenesis and Connective Tissue Research Groups, Department of Veterinary Preclinical Sciences, Faculty of Veterinary Science, University of Liverpool, Liverpool United Kingdom, 2School of Pharmacy and Chemistry, Liverpool John Moores University, Liverpool, United Kingdom, 3Department of Cellular and Molecular Pathology, Faculty of Medicine, University of Liverpool, Liverpool, United Kingdom and 4Institute of Anatomy, Charité Medicine University Berlin, Campus Benjamin Franklin, Berlin, Germany

Offprint requests to: Dr. A. Mobasheri, Molecular Pathogenesis and Connective Tissue Research Groups, Department of Veterinary Preclinical Sciences, Faculty of Veterinary Science, University of Liverpool, Liverpool L69 7ZJ, United Kingdom. Fax: +44 151 794 4243. e-mail: a.mobasheri@liverpool.ac.uk

 

Summary. Tissue microarrays (TMAs) are an ordered array of tissue cores on a glass slide. They permit immunohistochemical analysis of numerous tissue sections under identical experimental conditions. The arrays can contain samples of every organ in the human body, or a wide variety of common tumors and obscure clinical cases alongside normal controls. The arrays can also contain pellets of cultured tumor cell lines. These arrays may be used like any histological section for immunohistochemistry and in situ hybridization to detect protein and gene expression. This new technology will allow investigators to analyze numerous biomarkers over essentially identical samples, develop novel prognostic markers and validate potential drug targets. The ability to combine TMA technology with DNA microarrays and proteomics makes it a very attractive tool for analysis of gene expression in clinically stratified tumor specimens and relate expression of each particular protein with clinical outcome. Public domain software allows researchers to examine digital images of individual histological specimens from TMAs, evaluate and score them and store the quantitative data in a relational database. TMA technology may be specifically applied to the profiling of proteins of interest in other pathophysiological conditions such as congestive heart failure, renal disease, hypertension, diabetes, cystic fibrosis and neurodegenerative disorders. This review is intended to summarize the strengths and weaknesses of TMA technology which will have an increasingly important role in the laboratories of the post-genomic era. Histol. Histopathol. 19, 325-355 (2004)

Key words: Tissue microarray, Gene expression, Immunohistochemistry, In situ hybridization, Prognostic oncology, Cancer