Tissue Microarrays: Applications in Neuropathology Research, Diagnosis, and Education

Tissue microarrays (TMAs) are composite paraf‐fin blocks constructed by extracting cylindrical tissue core “biopsies” from different paraffin donor blocks and re‐embedding these into a single recipient (microarray) block at defined array coordinates. Using this technique, up to 1000 or more tissue samples can be composited into a single paraffin block. Tissue microarrays permit high‐volume simultaneous analysis of molecular targets at the DNA, mRNA, and protein levels under identical, standardized conditions on a single glass slide, and also provide maximal preservation and utilization of limited and irreplaceable archival tissue samples. This versatile technique facilitates retrospective and prospective human tissue studies, animal tissue studies, and cell line cytospin cell block studies. In this review, we present the technical aspects of TMA construction and sectioning, validation aspects of the technique, TMA advantages and limitations, and a sampling of the broad range of TMA uses in modern neuropathologic clinical diagnosis, research, and education. A specific illustration of the most widely employed and increasingly important TMA application is also presented: confirmation via TMA‐based immunohisto‐chemistry of the differential expression of a marker (IGFBP2) initially identified by gene expression pro‐filing to be overexpressed in glioblastoma.

[1]  R. T. Miller,et al.  Multitumor "sausage" blocks in immunohistochemistry. Simplified method of preparation, practical uses, and roles in quality assurance. , 1991, American journal of clinical pathology.

[2]  T. Yoshino,et al.  Reduction of hematopoietic cell-specific tyrosine phosphatase SHP-1 gene expression in natural killer cell lymphoma and various types of lymphomas/leukemias : combination analysis with cDNA expression array and tissue microarray. , 2001, The American journal of pathology.

[3]  Y. Chen,et al.  Detecting activation of ribosomal protein S6 kinase by complementary DNA and tissue microarray analysis. , 2000, Journal of the National Cancer Institute.

[4]  G. Parmigiani,et al.  Web-based tissue microarray image data analysis: initial validation testing through prostate cancer Gleason grading. , 2001, Human pathology.

[5]  E Mahlamäki,et al.  Hormone therapy failure in human prostate cancer: analysis by complementary DNA and tissue microarrays. , 1999, Journal of the National Cancer Institute.

[6]  D. Rimm,et al.  Validation of Tissue Microarray Technology in Breast Carcinoma , 2000, Laboratory Investigation.

[7]  T C Gasser,et al.  Survey of gene amplifications during prostate cancer progression by high-throughout fluorescence in situ hybridization on tissue microarrays. , 1999, Cancer research.

[8]  H. Moch,et al.  High-throughput tissue microarray analysis to evaluate genes uncovered by cDNA microarray screening in renal cell carcinoma. , 1999, The American journal of pathology.

[9]  J. Kononen,et al.  Tissue microarrays for high-throughput molecular profiling of tumor specimens , 1998, Nature Medicine.

[10]  C. Cordon-Cardo,et al.  Validation of tissue microarrays for immunohistochemical profiling of cancer specimens using the example of human fibroblastic tumors. , 2001, The American journal of pathology.

[11]  Holger Moch,et al.  Microarrays of bladder cancer tissue are highly representative of proliferation index and histological grade , 2001, The Journal of pathology.

[12]  W. Yung,et al.  Reactivation of insulin-like growth factor binding protein 2 expression in glioblastoma multiforme: a revelation by parallel gene expression profiling. , 1999, Cancer research.

[13]  J. Isola,et al.  High topoisomerase IIα expression associates with high proliferation rate and and poor prognosis in oligodendrogliomas , 2000, Neuropathology and applied neurobiology.

[14]  Axel Hoos,et al.  Tissue Microarray Profiling of Cancer Specimens and Cell Lines: Opportunities and Limitations , 2001, Laboratory Investigation.

[15]  L. Horvath,et al.  THE APPLICATION OF TISSUE MICROARRAYS TO CANCER RESEARCH , 2001, Pathology.

[16]  Georg Breier,et al.  Molecular Mechanisms of Developmental and Tumor Angiogenesis , 1994, Brain pathology.

[17]  O. Kallioniemi,et al.  Tissue microarray technology for high-throughput molecular profiling of cancer. , 2001, Human molecular genetics.

[18]  K. Plate,et al.  Vascular endothelial growth factor and glioma angiogenesis: coordinate induction of VEGF receptors, distribution of VEGF protein and possible in vivo regulatory mechanisms. , 1994, International journal of cancer.

[19]  S. Dhanasekaran,et al.  Delineation of prognostic biomarkers in prostate cancer , 2001, Nature.

[20]  M. Rubin,et al.  Tissue microarray assessment of prostate cancer tumor proliferation in African- American and white men. , 2000, Journal of the National Cancer Institute.

[21]  Georg Breier,et al.  Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo , 1992, Nature.

[22]  H. Moch,et al.  Tissue microarrays for gene amplification surveys in many different tumor types. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[23]  T Hardmeier,et al.  High-throughput tissue microarray analysis of cyclin E gene amplification and overexpression in urinary bladder cancer. , 2000, The American journal of pathology.

[24]  M. Rubin,et al.  Relational database structure to manage high-density tissue microarray data and images for pathology studies focusing on clinical outcome: the prostate specialized program of research excellence model. , 2001, The American journal of pathology.

[25]  H. Battifora The multitumor (sausage) tissue block: novel method for immunohistochemical antibody testing. , 1986, Laboratory investigation; a journal of technical methods and pathology.

[26]  M. Rubin,et al.  Neuroendocrine expression in metastatic prostate cancer: evaluation of high throughput tissue microarrays to detect heterogeneous protein expression. , 2000, Human pathology.

[27]  O. Kallioniemi,et al.  Identification of differentially expressed genes in human gliomas by DNA microarray and tissue chip techniques. , 2000, Cancer research.

[28]  D L Rimm,et al.  Amplification of tissue by construction of tissue microarrays. , 2001, Experimental and molecular pathology.