Tissue Microarray Profiling of Cancer Specimens and Cell Lines: Opportunities and Limitations

The implementations of high-throughput genetic technologies, such as oligonucleotide microarrays, generate myriad points of data. The identified potential candidate genes need to be further characterized and selected using a large number of well-characterized tumors and stringent criteria. Tissue microarrays allow for such high-throughput expression profiling of tumor samples, providing, in addition, information at the microanatomical level. Different techniques could be applied for identification of specific phenotypic (immunohistochemistry and in situ hybridization) or genotypic (fluorescence in situ hybridization) alterations, holding strong potential for translational research. Tissue microarrays consisting of 0.6-mm biopsies of paraffin-embedded tissues are well validated and have been used for various clinicopathological studies. This review discusses the technical considerations for construction of such arrays from paraffin-embedded tissues and cell lines and outlines their potential for clinical research applications. The use of paraffin-embedded tissues has some limitations with regard to analysis of RNA or certain proteins. To overcome such limitations, we have developed a cryoarray strategy allowing for the processing of multiple frozen tissue specimens and/or cell lines on a single tissue block. These approaches offer the opportunity to conduct pilot and validation studies of potential targets using clinical samples linked to clinicopathological databases.

[1]  Ronald W. Davis,et al.  Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarray , 1995, Science.

[2]  D. Mccormick.  Sequence the Human Genome , 1986, Bio/Technology.

[3]  Timothy B. Stockwell,et al.  The Sequence of the Human Genome , 2001, Science.

[4]  International Human Genome Sequencing Consortium.  Initial sequencing and analysis of the human genome , 2001, Nature.

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

[6]  M. Daly,et al.  MAPMAKER: an interactive computer package for constructing primary genetic linkage maps of experimental and natural populations. , 1987, Genomics.

[7]  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.

[8]  J. Sudbø,et al.  Gene-expression profiles in hereditary breast cancer. , 2001, The New England journal of medicine.

[9]  C. Cordon-Cardo.  Mutations of cell cycle regulators. Biological and clinical implications for human neoplasia. , 1995, The American journal of pathology.

[10]  Eric S. Lander,et al.  Faster Multipoint Linkage Analysis Using Fourier Transforms , 1998, J. Comput. Biol..

[11]  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.

[12]  S. Groshen,et al.  Elevated and absent pRb expression is associated with bladder cancer progression and has cooperative effects with p53. , 1998, Cancer research.

[13]  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.

[14]  E. Winzeler,et al.  Genomics, gene expression and DNA arrays , 2000, Nature.

[15]  C. Antonescu,et al.  Characterization of molecular abnormalities in human fibroblastic neoplasms: a model for genotype-phenotype association in soft tissue tumors. , 2001, Cancer research.

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

[17]  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.

[18]  D. Lockhart,et al.  Expression monitoring by hybridization to high-density oligonucleotide arrays , 1996, Nature Biotechnology.

[19]  Satoru Miyano,et al.  Inferring qualitative relations in genetic networks and metabolic pathways , 2000, Bioinform..

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

[21]  C. Cordon-Cardo,et al.  Prognostic implications of p53 nuclear overexpression and high proliferation index of Ki-67 in adult soft-tissue sarcomas. , 1994, Journal of the National Cancer Institute.

[22]  G D Schuler,et al.  Molecular profiling of clinical tissue specimens: feasibility and applications. , 2000, The American journal of pathology.

[23]  G D Schuler,et al.  Molecular profiling of clinical tissues specimens: feasibility and applications. , 2000, The Journal of molecular diagnostics : JMD.

[24]  S. P. Fodor,et al.  High density synthetic oligonucleotide arrays , 1999, Nature Genetics.

[25]  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.