Abstract
High-throughput technologies have been developed in the hope of increasing the pace of biomedical research, and accelerating the rate of translation from bench to bedside. Using such technology in target discovery has resulted in the need for systematic validation of the targets in an equally rapid manner. For example, gene expression microarrays have highlighted many potential targets in cancer, and tissue microarrays have emerged as a powerful tool to validate these targets by measuring tumor-specific protein expression and linking it to clinical outcome. Automated quantitative analysis of the tissue microarray 'spots' is beginning to take the technology a step further, removing observer bias, and providing standards for quality control and the potential for high-throughput analysis. The validation required for translation of tissue biomarkers from the research lab to the clinical lab will probably rely heavily on the combination of tissue microarray technology with automated quantitative analysis.
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References
Battifora H (1986) The multitumor (sausage) tissue block: novel method for immunohistochemical antibody testing. Lab Invest 55: 244–248
Wan WH et al. (1987) A rapid and efficient method for testing immunohistochemical reactivity of monoclonal antibodies against multiple tissue samples simultaneously. J Immunol Methods 103: 121–129
Kononen J et al. (1998) Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 4: 844–847
Rimm DL et al. (2001) Tissue microarray: a new technology for amplification of tissue resources. Cancer J 7: 24–31
Chung CH et al. (2002) Molecular portraits and the family tree of cancer. Nat Genet 32 (Suppl): 533–540
van de Rijn M and Gilks CB (2004) Applications of microarrays to histopathology. Histopathology 44: 97–108
Bertucci F et al. (2004) Gene expression profiling of colon cancer by DNA microarrays and correlation with histoclinical parameters. Oncogene 23: 1377–1391
Dhanasekaran SM et al. (2001) Delineation of prognostic biomarkers in prostate cancer. Nature 412: 822–826
Moch H et al. (1999) High-throughput tissue microarray analysis to evaluate genes uncovered by cDNA microarray screening in renal cell carcinoma. Am J Pathol 154: 981–986
Sallinen SL et al. (2000) Identification of differentially expressed genes in human gliomas by DNA microarray and tissue chip techniques. Cancer Res 60: 6617–6622
Hans CP et al. (2004) Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103: 275–282
Rhodes A et al. (2002) A formalin-fixed, paraffin-processed cell line standard for quality control of immunohistochemical assay of HER-2/neu expression in breast cancer. Am J Clin Pathol 117: 81–89
Want R (2004) RFID. A key to automating everything. Sci Am 290: 56–65
Garcia JF et al. (2003) Hodgkin and Reed-Sternberg cells harbor alterations in the major tumor suppressor pathways and cell-cycle checkpoints: analyses using tissue microarrays. Blood 101: 681–689
Nocito A et al. (2001) Microarrays of bladder cancer tissue are highly representative of proliferation index and histological grade. J Pathol 194: 349–357
Camp RL et al. (2000) Validation of tissue microarray technology in breast carcinoma. Lab Invest 80: 1943–1949
Hendriks Y et al. (2003) Conventional and tissue microarray immunohistochemical expression analysis of mismatch repair in hereditary colorectal tumors. Am J Pathol 162: 469–477
Leversha MA et al. (2003) Expression of p53, pRB, and p16 in lung tumours: a validation study on tissue microarrays. J Pathol 200: 610–619
Engellau J et al. (2001) Tissue microarray technique in soft tissue sarcoma: immunohistochemical Ki-67 expression in malignant fibrous histiocytoma. Appl Immunohistochem Mol Morphol 9: 358–363
Schraml P et al. (1999) Tissue microarrays for gene amplification surveys in many different tumor types. Clin Cancer Res 5: 1966–1975
Torhorst J et al. (2001) Tissue microarrays for rapid linking of molecular changes to clinical endpoints. Am J Pathol 159: 2249–2256
Rubin MA et al. (2002) Tissue microarray sampling strategy for prostate cancer biomarker analysis. Am J Surg Pathol 26: 312–319
Theillet C (1998) Full speed ahead for tumor screening. Nat Med 4: 767–768
McCarty KS Jr et al. (1986) Use of a monoclonal anti-estrogen receptor antibody in the immunohistochemical evaluation of human tumors. Cancer Res 46 (Suppl): S4244–S4248
Harvey JM et al. (1999) Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol 17: 1474–1481
Wang S et al. (2001) Assessment of HER-2/neu status in breast cancer. Automated Cellular Imaging System (ACIS)-assisted quantitation of immunohistochemical assay achieves high accuracy in comparison with fluorescence in situ hybridization assay as the standard. Am J Clin Pathol 116: 495–503
Sauter G et al. (2003) Tissue microarrays in drug discovery. Nat Rev Drug Discov 2: 962
Simon R and Sauter G (2003) Tissue microarray (TMA) applications: implications for molecular medicine. Expert Rev Mol Med 2003: 1–12
Jubb AM (2003) Quantitative analysis of colorectal tissue microarrays by immunofluorescence and in situ hybridization. J Pathol 200: 577–588
Camp RL et al. (2002) Automated subcellular localization and quantification of protein expression in tissue microarrays. Nat Med 8: 1323–1327
Camp RL et al. (2003) Quantitative analysis of breast cancer tissue microarrays shows that both high and normal levels of HER2 expression are associated with poor outcome. Cancer Res 63: 1445–1448
Berger A et al. Automated Quantitative Analysis (AQUA) of HDM2 Expression in Malignant Melanoma Shows Association with Early Stage Disease and Improved Outcome. Cancer Res, in press
Rubin MA et al. (2004) Quantitative determination of expression of the prostate cancer protein alpha-methylacyl-CoA racemase using automated quantitative analysis (AQUA): a novel paradigm for automated and continuous biomarker measurements. Am J Pathol 164: 831–840
Simon R et al. (2003) Tissue microarrays in cancer diagnosis. Expert Rev Mol Diagn 3: 421–430
Hammond ME and Taube SE (2002) Issues and barriers to development of clinically useful tumor markers: a development pathway proposal. Semin Oncol 29: 213–221
Press MF et al. (2002) Evaluation of HER-2/neu gene amplification and overexpression: comparison of frequently used assay methods in a molecularly characterized cohort of breast cancer specimens. J Clin Oncol 20: 3095–3105
Barker PE (2003) Cancer biomarker validation: standards and process: roles for the National Institute of Standards and Technology (NIST). Ann N Y Acad Sci 983: 142–150
Zerhouni E (2003) Medicine. The NIH Roadmap. Science 302: 63–72
Sullivan Pepe M et al. (2001) Phases of biomarker development for early detection of cancer. J Natl Cancer Inst 93: 1054–1061
Alkushi A et al. (2003) Immunoprofile of cervical and endometrial adenocarcinomas using a tissue microarray. Virchows Archiv 442: 271–277
Chung GG et al. (2004) beta-Catenin and p53 analyses of a breast carcinoma tissue microarray. Cancer 100: 2084–2092
Barlund M et al. (2000) Multiple genes at 17q23 undergo amplification and overexpression in breast cancer. Cancer Res 60: 5340–5344
Chung GG et al. (2001) Tissue microarray analysis of beta-catenin in colorectal cancer shows nuclear phospho-beta-catenin is associated with a better prognosis. Clin Cancer Res 7: 4013–4020
Alonso SR et al. (2004) Progression in cutaneous malignant melanoma is associated with distinct expression profiles: a tissue microarray-based study. Am J Pathol 164: 193–203
Bubendorf L et al. (1999) Survey of gene amplifications during prostate cancer progression by high-throughout fluorescence in situ hybridization on tissue microarrays. Cancer Res 59: 803–806
Makretsov N et al. (2004) Hierarchical clustering analysis of tissue microarray immunostaining data identifies prognostically significant groups of breast cancer. Clin Cancer Res 10: 6143–6151
Nishizuka S et al. (2003) Diagnostic markers that distinguish colon and ovarian adenocarcinomas: identification by genomic, proteomic, and tissue array profiling. Cancer Res 63: 5243–5250
Acknowledgements
J Giltnane is supported by NIH/NIGMS Medical Scientist Training Program Grant GM07205 (JG). D Rimm is supported by a grant from the Patrick and Catherine Weldon Donaghue Foundation for Medical Research, and grants from the NIH (R21 CA 100825 and R33 CA 106709), the US Army (DAMD-17-02-0463 and DAMD17-02-1-0634) and the Greenwich Breast Cancer Alliance. The authors acknowledge Bonnie King for FISH and Malini Harigopal for mRNA-ISH images.
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J Giltnane declared she has no competing interests.
D Rimm is a founder, stockholder and consultant to HistoRx, the Yale licensee of AQUA™ technology.
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Giltnane, J., Rimm, D. Technology Insight: identification of biomarkers with tissue microarray technology. Nat Rev Clin Oncol 1, 104–111 (2004). https://doi.org/10.1038/ncponc0046
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DOI: https://doi.org/10.1038/ncponc0046
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