Skip to main content

Tissue Microarray

  • Chapter
  • First Online:
Handbook of Practical Immunohistochemistry

Abstract

Tissue microarray (TMA) is a powerful tool for performing population level studies using tissues routinely processed in surgical pathology and cytopathology cell blocks. TMA construction can be done manually or with semiautomated and fully automated equipment on formalin fixed, paraffin embedded (FFPE) tissue produced in routine histology. A variety of other processed materials may also be used, including frozen tissue, cell culture lines, and resin embedded tissue. TMAs are used for a variety of applications including the validation of cDNA array data; validation of the sensitivity and specificity of antibodies; quality assurance in immunohistochemistry; translation of data from cell line, xenograft, and animal models to human cancer; collaborative studies, especially for the aggregation and preservation of rare tumor tissues; molecular profiling of large series of tumors or diseased tissue and correlation with clinical endpoints; and evaluation of diagnostic, prognostic, and therapeutic potential of newly discovered genes and molecules. Most standard histologic and molecular techniques can be applied to TMA sections. Optimal storage conditions of TMA blocks and sections in order to preserve antigenicity continue to be an issue. Image analysis and data management are crucial issues, but many tools are available.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kallioniemi OP, Wagner U, Kononen J, Sauter G. Tissue microarray technology for high-throughput molecular profiling of cancer. Hum Mol Genet. 2001;10(7):657–62.

    Article  CAS  PubMed  Google Scholar 

  2. Nocito A, Kononen J, Kallioniemi OP, Sauter G. Tissue microarrays (TMAs) for high-throughput molecular pathology research. Int J Cancer. 2001;94(1):1–5.

    Article  CAS  PubMed  Google Scholar 

  3. Torhorst J, Bucher C, Kononen J, Haas P, Zuber M, Kochli OR, et al. Tissue microarrays for rapid linking of molecular changes to clinical endpoints. Am J Pathol. 2001;159(6):2249–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Bubendorf L. High-throughput microarray technologies: from genomics to clinics. Eur Urol. 2001;40(2):231–8.

    Article  CAS  PubMed  Google Scholar 

  5. Simon R, Mirlacher M, Sauter G. Tissue microarrays in cancer diagnosis. Expert Rev Mol Diagn. 2003;3(4):421–30.

    Article  CAS  PubMed  Google Scholar 

  6. Simon R, Sauter G. Tissue microarrays for miniaturized high-throughput molecular profiling of tumors. Exp Hematol. 2002;30(12):1365–72.

    Article  CAS  PubMed  Google Scholar 

  7. Skacel M, Skilton B, Pettay JD, Tubbs RR. Tissue microarrays: a powerful tool for high-throughput analysis of clinical specimens: a review of the method with validation data. Appl Immunohistochem Mol Morphol. 2002;10(1):1–6.

    CAS  PubMed  Google Scholar 

  8. Conway C, Dobson L, O’Grady A, Kay E, Costello S, O’Shea D. Virtual microscopy as an enabler of automated/quantitative assessment of protein expression in TMAs. Histochem Cell Biol. 2008;130(3):447–63.

    Article  CAS  PubMed  Google Scholar 

  9. Moch H, Kononen T, Kallioniemi OP, Sauter G. Tissue microarrays: what will they bring to molecular and anatomic pathology? Adv Anat Pathol. 2001;8(1):14–20.

    Article  CAS  PubMed  Google Scholar 

  10. Al Kuraya K, Simon R, Sauter G. Tissue microarrays for high-throughput molecular pathology. Ann Saudi Med. 2004;24(3):169–74.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Simon R. Applications of tissue microarray technology. Methods Mol Biol. 2010;664:1–16.

    Article  CAS  PubMed  Google Scholar 

  12. Franco R, Caraglia M, Facchini G, Abbruzzese A, Botti G. The role of tissue microarray in the era of target-based agents. Expert Rev Anticancer Ther. 2011;11(6):859–69.

    Article  CAS  PubMed  Google Scholar 

  13. Hewitt SM. The application of tissue microarrays in the validation of microarray results. Methods Enzymol. 2006;410:400–15.

    Article  CAS  PubMed  Google Scholar 

  14. Watanabe A, Cornelison R, Hostetter G. Tissue microarrays: applications in genomic research. Expert Rev Mol Diagn. 2005;5(2):171–81.

    Article  CAS  PubMed  Google Scholar 

  15. Brown LA, Huntsman D. Fluorescent in situ hybridization on tissue microarrays: challenges and solutions. J Mol Histol. 2007;38(2):151–7.

    Article  CAS  PubMed  Google Scholar 

  16. Caldwell ML, Moffitt RA, Liu J, Parry RM, Sharma Y, Wang MD. Simple quantification of multiplexed quantum dot staining in clinical tissue samples. Annu Int Conf IEEE Eng Med Biol Soc. 2008;2008:1907–10.

    PubMed  Google Scholar 

  17. Ghazani AA, Lee JA, Klostranec J, Xiang Q, Dacosta RS, Wilson BC, et al. High throughput quantification of protein expression of cancer antigens in tissue microarray using quantum dot nanocrystals. Nano Lett. 2006;6(12):2881–6.

    Article  CAS  PubMed  Google Scholar 

  18. Takikita M, Chung JY, Hewitt SM. Tissue microarrays enabling high-throughput molecular pathology. Curr Opin Biotechnol. 2007;18(4):318–25.

    Article  CAS  PubMed  Google Scholar 

  19. Chung JY, Braunschweig T, Baibakov G, Galperin M, Ramesh A, Skacel M, et al. Transfer and multiplex immunoblotting of a paraffin embedded tissue. Proteomics. 2006;6(3):767–74.

    Article  CAS  PubMed  Google Scholar 

  20. Chung JY, Braunschweig T, Tuttle K, Hewitt SM. Tissue microarrays as a platform for proteomic investigation. J Mol Histol. 2007;38(2):123–8.

    Article  CAS  PubMed  Google Scholar 

  21. Schweizer MS, Schumacher L, Rubin MA. Constructing tissue microarrays for research use. Curr Protoc Hum Genet. 2004;Chapter 10:Unit 10.7.

    PubMed  Google Scholar 

  22. Zimpfer A, Schonberg S, Lugli A, Agostinelli C, Pileri SA, Went P, et al. Construction and validation of a bone marrow tissue microarray. J Clin Pathol. 2007;60(1):57–61.

    Article  PubMed  Google Scholar 

  23. Hewitt SM. Design, construction, and use of tissue microarrays. Methods Mol Biol. 2004;264:61–72.

    CAS  PubMed  Google Scholar 

  24. Albanghali M, Green A, Rakha E, Aleskandarany M, Nolan C, Ellis I, et al. Construction of tissue microarrays from core needle biopsies – a systematic literature review. Histopathology. 2016;68(3):323–32.

    Article  PubMed  Google Scholar 

  25. Lacombe A, Carafa V, Schneider S, Sticker-Jantscheff M, Tornillo L, Eppenberger-Castori S. Re-punching tissue microarrays is possible: why can this be useful and how to do it. Microarrays. 2015;4(2):245–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Toth L, Nagy B, Mehes G, Laszlo E, Molnar PP, Poka R, et al. Cell adhesion molecule profiles, proliferation activity and p53 expression in advanced epithelial ovarian cancer induced malignant ascites-correlation of tissue microarray and cytology microarray. Pathol Res Pract. 2018;214(7):978–85.

    Article  CAS  PubMed  Google Scholar 

  27. Sexton T, Kucera GL, Levine EA, Watabe K, O’Neill SS. Optimization of tissue microarrays from banked human formalin-fixed paraffin embedded tissues in the cancer research setting. Biopreserv Biobank. 2019;17(5):452–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kramer MW, Merseburger AS, Hennenlotter J, Kuczyk M. Tissue microarrays in clinical urology--technical considerations. Scand J Urol Nephrol. 2007;41(6):478–84.

    Article  CAS  PubMed  Google Scholar 

  29. Bingle L, Fonseca FP, Farthing PM. Constructing tissue microarrays: protocols and methods considering potential advantages and disadvantages for downstream use. Methods Mol Biol. 2017;1537:429–38.

    Article  CAS  PubMed  Google Scholar 

  30. Zhou L, Hodeib M, Abad JD, Mendoza L, Kore AR, Hu Z. New tissue microarray technology for analyses of gene expression in frozen pathological samples. BioTechniques. 2007;43(1):101–5.

    Article  CAS  PubMed  Google Scholar 

  31. Hu Z, Chang E, Hodeib M. An alternative technology to prepare tissue microarray using frozen tissue samples. Methods Mol Biol. 2010;664:81–91.

    Article  CAS  PubMed  Google Scholar 

  32. Avninder S, Ylaya K, Hewitt SM. Tissue microarray: a simple technology that has revolutionized research in pathology. J Postgrad Med. 2008;54(2):158–62.

    Article  CAS  PubMed  Google Scholar 

  33. Schoenberg Fejzo M, Slamon DJ. Frozen tumor tissue microarray technology for analysis of tumor RNA, DNA, and proteins. Am J Pathol. 2001;159(5):1645–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hoos A, Cordon-Cardo C. Tissue microarray profiling of cancer specimens and cell lines: opportunities and limitations. Lab Investig. 2001;81(10):1331–8.

    Article  CAS  PubMed  Google Scholar 

  35. Howat WJ, Wilson. Tissue fixation and the effect of molecular fixatives on downstream staining procedures. Methods (Duluth). 2014;70(1):12–9.

    Article  CAS  Google Scholar 

  36. Fedor HL, De Marzo AM. Practical methods for tissue microarray construction. Methods Mol Med. 2005;103:89–101.

    CAS  PubMed  Google Scholar 

  37. Andersson AC, Stromberg S, Backvall H, Kampf C, Uhlen M, Wester K, et al. Analysis of protein expression in cell microarrays: a tool for antibody-based proteomics. J Histochem Cytochem. 2006;54(12):1413–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Hu Q, Shi Y, Li X, Hou Y, Jiang D, Huang J, et al. An improved high-output cell microarray technology. Cytopathology. 2015;26(1):44–9.

    Article  CAS  PubMed  Google Scholar 

  39. Henshall S. Tissue microarrays. J Mammary Gland Biol Neoplasia. 2003;8(3):347–58.

    Article  PubMed  Google Scholar 

  40. Rui H, LeBaron MJ. Creating tissue microarrays by cutting-edge matrix assembly. Expert Rev Med Devices. 2005;2(6):673–80.

    Article  CAS  PubMed  Google Scholar 

  41. Deng FM, Zhao Y, Kong X, Lee P, Melamed J. Construction of tissue microarrays using pre-existing slides as source of tissue when paraffin blocks are unavailable. J Clin Pathol. 2013;66(7):627–9.

    Article  CAS  PubMed  Google Scholar 

  42. Packeisen J, Korsching E, Herbst H, Boecker W, Buerger H. Demystified…tissue microarray technology. Mol Pathol. 2003;56(4):198–204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. van den Broek LJ, van de Vijver MJ. Assessment of problems in diagnostic and research immunohistochemistry associated with epitope instability in stored paraffin sections. Appl Immunohistochem Mol Morphol. 2000;8(4):316–21.

    PubMed  Google Scholar 

  44. Anagnostou VK, Lowery FJ, Syrigos KN, Cagle PT, Rimm DL. Quantitative evaluation of protein expression as a function of tissue microarray core diameter: is a large (1.5 mm) core better than a small (0.6 mm) core? Arch Pathol Lab Med. 2010;134(4):613–9.

    Article  PubMed  Google Scholar 

  45. Eskaros AR, Egloff SA, Boyd KL, Richardson JE, Hyndman ME, Zijlstra A. Larger core size has superior technical and analytical accuracy in bladder tissue microarray. Lab Investig. 2017;97(3):335–42.

    Article  CAS  PubMed  Google Scholar 

  46. de Jong D, Xie W, Rosenwald A, Chhanabhai M, Gaulard P, Klapper W, et al. Immunohistochemical prognostic markers in diffuse large B-cell lymphoma: validation of tissue microarray as a prerequisite for broad clinical applications (a study from the Lunenburg Lymphoma Biomarker Consortium). J Clin Pathol. 2009;62(2):128–38.

    Article  PubMed  Google Scholar 

  47. Fons G, Hasibuan SM, van der Velden J, ten Kate FJ. Validation of tissue microarray technology in endometrioid cancer of the endometrium. J Clin Pathol. 2007;60(5):500–3.

    Article  CAS  PubMed  Google Scholar 

  48. Camp RL, Neumeister V, Rimm DL. A decade of tissue microarrays: progress in the discovery and validation of cancer biomarkers. J Clin Oncol. 2008;26(34):5630–7.

    Article  PubMed  Google Scholar 

  49. Warnberg F, Amini RM, Goldman M, Jirstrom K. Quality aspects of the tissue microarray technique in a population-based cohort with ductal carcinoma in situ of the breast. Histopathology. 2008;53(6):642–9.

    Article  CAS  PubMed  Google Scholar 

  50. Kyndi M, Sorensen FB, Knudsen H, Overgaard M, Nielsen HM, Andersen J, et al. Tissue microarrays compared with whole sections and biochemical analyses. A subgroup analysis of DBCG 82 b&c. Acta Oncol. 2008;47(4):591–9.

    Article  CAS  PubMed  Google Scholar 

  51. Hecht JL, Kotsopoulos J, Gates Hankinson SE, Tworoger SS. Validation of tissue microarray technology in ovarian cancer: results from the Nurses’ Health Study. Cancer Epidemiol Biomark Prev. 2008;17(11):3043–50.

    Article  CAS  Google Scholar 

  52. Mirlacher M, Simon R. Recipient block TMA technique. Methods Mol Biol. 2010;664:37–44.

    Article  CAS  PubMed  Google Scholar 

  53. Tennstedt P, Koster P, Bruchmann A, Mirlacher M, Haese A, Steuber T, et al. The impact of the number of cores on tissue microarray studies investigating prostate cancer biomarkers. Int J Oncol. 2012;40(1):261–8.

    PubMed  Google Scholar 

  54. Jones S, Prasad ML. Comparative evaluation of high-throughput small-core (0.6-mm) and large-core (2-mm) thyroid tissue microarray: is larger better? Arch Pathol Lab Med. 2012;136(2):199–203.

    Article  PubMed  Google Scholar 

  55. Linderoth J, Ehinger M, Akerman M, CavallinStahl E, Enblad G, Erlanson M, et al. Tissue microarray is inappropriate for analysis of BCL6 expression in diffuse large B-cell lymphoma. Eur J Haematol. 2007;79(2):146–9.

    Article  PubMed  Google Scholar 

  56. Schmidt LH, Biesterfeld S, Kummel A, Faldum A, Sebastian M, Taube C, et al. Tissue microarrays are reliable tools for the clinicopathological characterization of lung cancer tissue. Anticancer Res. 2009;29(1):201–9.

    PubMed  Google Scholar 

  57. Henriksen KL, Rasmussen BB, Lykkesfeldt AE, Moller S, Ejlertsen B, Mouridsen HT. Semi-quantitative scoring of potentially predictive markers for endocrine treatment of breast cancer: a comparison between whole sections and tissue microarrays. J Clin Pathol. 2007;60(4):397–404.

    Article  PubMed  Google Scholar 

  58. Pu RT, Giordano TJ, Michael CW. Utility of cytology microarray constructed from effusion cell blocks for immunomarker validation. Cancer. 2008;114(5):300–6.

    Article  PubMed  Google Scholar 

  59. Simon R, Mirlacher M, Sauter G. Tissue microarrays. Methods Mol Med. 2005;114:257–68.

    CAS  PubMed  Google Scholar 

  60. Tzankov A, Went P, Zimpfer A, Dirnhofer S. Tissue microarray technology: principles, pitfalls and perspectives--lessons learned from hematological malignancies. Exp Gerontol. 2005;40(8–9):737–44.

    Article  CAS  PubMed  Google Scholar 

  61. Eguiluz C, Viguera E, Millan L, Perez J. Multitissue array review: a chronological description of tissue array techniques, applications and procedures. Pathol Res Pract. 2006;202(8):561–8.

    Article  CAS  PubMed  Google Scholar 

  62. Bertheau P, CazalsHatem D, Meignin V, de Roquancourt A, Verola O, Lesourd A, et al. Variability of immunohistochemical reactivity on stored paraffin slides. J Clin Pathol. 1998;51(5):370–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Mirlacher M, Kasper M, Storz M, Knecht Y, Durmuller U, Simon R, et al. Influence of slide aging on results of translational research studies using immunohistochemistry. Mod Pathol. 2004;17(11):1414–20.

    Article  PubMed  Google Scholar 

  64. Karlsson C, Karlsson MG. Effects of long-term storage on the detection of proteins, DNA, and mRNA in tissue microarray slides. J. Histochem. Cytochem. 2011;59(12):1113–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Xie R, Chung JY, Ylaya K, Williams RL, Guerrero N, Nakatsuka N, et al. Factors influencing the degradation of archival formalin-fixed paraffin-embedded tissue sections. J Histochem Cytochem. 2011;59(4):356–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Fergenbaum JH, Garcia-Closas M, Hewitt SM, Lissowska J, Sakoda LC, Sherman ME. Loss of antigenicity in stored sections of breast cancer tissue microarrays. Cancer Epidemiol Biomark Prev. 2004;13(4):667–72.

    Article  CAS  Google Scholar 

  67. Jacobs TW, Prioleau JE, Stillman IE, Schnitt SJ. Loss of tumor marker-immunostaining intensity on stored paraffin slides of breast cancer. J Natl Cancer Inst. 1996;88(15):1054–9.

    Article  CAS  PubMed  Google Scholar 

  68. Andeen NK, Bowman R, Baullinger T, Brooks JM, Tretiakova MS. Epitope preservation methods for tissue microarrays: longitudinal prospective study. Am J Clin Pathol. 2017;148(5):380–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Omilian AR, Zirpoli GR, Cheng TD, Yao S, Stein L, Davis W, et al. Storage conditions and immunoreactivity of breast cancer subtyping markers in tissue microarray sections. Appl Immunohistochem Mol Morphol. 2020;28(4):267–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Berman JJ, Edgerton ME, Friedman BA. The tissue microarray data exchange specification: a community-based, open source tool for sharing tissue microarray data. BMC Med Inform Decis Mak. 2003;3:5.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Lee HW, Park YR, Sim J, Park RW, Kim WH, Kim JH. The tissue microarray object model: a data model for storage, analysis, and exchange of tissue microarray experimental data. Arch Pathol Lab Med. 2006;130(7):1004–13.

    Article  CAS  PubMed  Google Scholar 

  72. Marinelli RJ, Montgomery K, Liu CL, Shah NH, Prapong W, Nitzberg M, et al. The Stanford tissue microarray database. Nucleic Acids Res. 2008;36(Database issue):871–7.

    Google Scholar 

  73. Loughrey MB, Bankhead P, Coleman HG, Hagan RS, Craig S, McCorry A, et al. Validation of the systematic scoring of immunohistochemically stained tumour tissue microarrays using QuPath digital image analysis. Histopathology. 2018;73(2):327–38.

    Article  PubMed  Google Scholar 

  74. Au NH, Cheang M, Huntsman DG, Yorida E, Coldman A, Elliott WM, et al. Evaluation of immunohistochemical markers in non-small cell lung cancer by unsupervised hierarchical clustering analysis: a tissue microarray study of 284 cases and 18 markers. J Pathol. 2004;204(1):101–9.

    Article  CAS  PubMed  Google Scholar 

  75. Hsu FD, Nielsen TO, Alkushi A, Dupuis B, Huntsman D, Liu CL, et al. Tissue microarrays are an effective quality assurance tool for diagnostic immunohistochemistry. Mod Pathol. 2002;15(12):1374–80.

    Article  PubMed  Google Scholar 

  76. Makretsov NA, Huntsman DG, Nielsen TO, Yorida E, Peacock M, Cheang MC, et al. Hierarchical clustering analysis of tissue microarray immunostaining data identifies prognostically significant groups of breast carcinoma. Clin Cancer Res. 2004;10(18 Pt 1):6143–51.

    Article  CAS  PubMed  Google Scholar 

  77. Demichelis F, Magni P, Piergiorgi P, Rubin MA, Bellazzi R. A hierarchical Naive Bayes Model for handling sample heterogeneity in classification problems: an application to tissue microarrays. BMC Bioinform. 2006;7:514.

    Article  CAS  Google Scholar 

  78. Breiman L. Random forests. Mach Learn. 2001;45(1):5–32.

    Article  Google Scholar 

  79. Conway CM, O’Shea D, O’Brien S, Lawler DK, Dodrill GD, O’Grady A, et al. The development and validation of the Virtual Tissue Matrix, a software application that facilitates the review of tissue microarrays on line. BMC Bioinform. 2006;7:256.

    Article  CAS  Google Scholar 

  80. Simon R, Sauter G. Tissue microarray (TMA) applications: implications for molecular medicine. Expert Rev Mol Med. 2003;5(26):1–12.

    Article  PubMed  Google Scholar 

  81. Foran DJ, Chen W, Yang L. Automated image interpretation and computer-assisted diagnostics. Stud Health Technol Inform. 2013;185:77–108.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Myra L. Wilkerson .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Geisinger Clinic

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Wilkerson, M.L., Hewitt, S. (2022). Tissue Microarray. In: Lin, F., Prichard, J.W., Liu, H., Wilkerson, M.L. (eds) Handbook of Practical Immunohistochemistry. Springer, Cham. https://doi.org/10.1007/978-3-030-83328-2_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-83328-2_11

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-83327-5

  • Online ISBN: 978-3-030-83328-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics