Advertisement

A Practical Guide to Constructing and Using Tissue Microarrays

Protocol
First Online:
Part of the Methods in Molecular Biology book series (MIMB, volume 675)

Abstract

Tissue microarray (TMA) technology is a robust “high throughput” method of tissue analysis, whereby a large number of patient samples can be examined in a short time using a minimum number of slides. In a TMA, cylinders of tissue are cored out of formalin-fixed, paraffin-embedded tissue blocks and slotted in a regular grid pattern into a blank recipient paraffin wax block. The TMA block is then cut using a standard laboratory microtome. Sections generated are suitable for all in situ techniques, such as immunohistochemistry (IHC) and in situ hybridisation, using essentially the same protocols as are used in conventional sections. The principle advantages of TMAs are that they save valuable biological material and ensure more reproducible reaction conditions while at the same time reducing re-agent costs and laboratory processing. Immunohistochemical studies designed to examine the prognostic utility of TMAs compared with large sections have generally found that they are comparable.

Key words

Tissue microarray Tissue core Image analysis Antigen heterogeneity Immuno­his­tochemistry 
This is a preview of subscription content, log in to check access.

References

  1. 1.
    Gulmann, C., Loring, P., O’Grady, A., and Kay, E. (2004) Miniature tissue microarrays for HercepTest standardisation and analysis. J Clin Path 57, 1229–1231.PubMedCrossRefGoogle Scholar
  2. 2.
    Nielsen, T.O., Hsu, F.D., Jensen, K., Cheang, M., Karaca, G., Hu, Z., et al. (2004) Immunohistochemical and clinical characterisation of the basal-like subtype of invasive breast carcinoma. Clin Ca Res 10, 5367–5374.CrossRefGoogle Scholar
  3. 3.
    Deutsch, E.W., Ball, C.A., Bova, G.S., Brazma, A., Bumgarner R.E., Campbell, D., et al. (2006) Development of the minimum information specification for in situ hybridization and immunohistochemistry experiments (MISFISHIE). OMICS 10, 205–208.PubMedCrossRefGoogle Scholar
  4. 4.
    Camp, R.L., Chung, G.G., and Rimm, D.L. (2002) Automated subcellular localization and quantification of protein expression in tissue microarrays. Nature Medicine 8, 1323–1328.PubMedCrossRefGoogle Scholar
  5. 5.
    Jhavar, S., Corbishley, C.M., Dearnaley, D., Fisher, C., Falconer, A., Parker, C., et al. (2004) Construction of tissue microarrays from prostate needle biopsy specimens. Br J Cancer 93, 478–482.CrossRefGoogle Scholar
  6. 6.
    Yang, X.R., Charette, L.A., Garcia-Closas, M, Lissowska, J., Paal, E., Sidawy, M., et al. (2006) Construction and validation of tissue microarrays of ductal carcinoma in situ and terminal duct lobular units associated with invasive breast carcinoma. Diagn Mol Pathol 15, 157–162.PubMedCrossRefGoogle Scholar
  7. 7.
    DiVito, K.A., Berger, A.J., Camp, R.L., Dolled-Filhart, M., Rimm, D.L., and Kluger, H.M. (2004) Automated quantitative analysis of tissue microarrays reveals an association between high Bcl-2 expression and improved outcome in melanoma. Cancer Res 64, 8773–8777.PubMedCrossRefGoogle Scholar
  8. 8.
    Aubele, M., Mattis, A., Zitzelsberger, H., Walck, A., Kremer, M., Hutzler, P., et al. (1999) Intratumoral heterogeneity in breast carcinoma revealed by laser-microdissection and comparative genomic hybridisation. Cancer Genet Cytogenet 110, 94–102.PubMedCrossRefGoogle Scholar
  9. 9.
    Trudel, M., Mulligan, L., Cavenee, W., Margolese, R., Cote, J., and Gariepy, G. (1992) Retinoblastoma and p53 gene product expression­ in breast carcinoma. Hum Pathol 23, 1388–1394.PubMedCrossRefGoogle Scholar
  10. 10.
    Quirke, P., Dyson, J.E.D., Dixon, M.F., Bird, C.C., and Joslin, C.A.F. (1985) Heterogeneity of colorectal adenocarcinomas evaluated by flow cytometry and histopathology. Br J Cancer 51, 99–106.PubMedCrossRefGoogle Scholar
  11. 11.
    Losi, L., Baisse, B., Bouzourene, H., and Benhattar, J. (2005) Evolution of intratumoral genetic heterogeneity during colorectal cancer progression. Carcinogenesis 26, 916–922.PubMedCrossRefGoogle Scholar
  12. 12.
    Samowitz, W.S., and Slattery, M.L. (1999) Regional reproducibility of microsatellite instability in sporadic colorectal cancer. Genes Chromosomes Cancer 26, 106–114.PubMedCrossRefGoogle Scholar
  13. 13.
    Torhorst, J., Bucher, C., Kononen, J., Haas, P., Zuber, M., Kochli, O.R., et al. (2001) Tissue microarrays for rapid linking of molecular changes to clinical endpoints. Am J Pathol 159, 2249–2256.PubMedCrossRefGoogle Scholar
  14. 14.
    Aaltonen, K., Ahlin, C., Amini, R.M., Salonen, L., Fjallskog, M.L., Heikkila, P., et al. (2006) Reliability of cyclin A assessment on tissue microarrays in breast cancer compared to conventional histological slides. Br J Cancer 94, 1697–1702.PubMedGoogle Scholar
  15. 15.
    Bhargava, R., Gerald, W.L., Li, A.R., Pan, Q., Lal, P., Ladanyi, M., et al. (2005) EGFR gene amplification in breast cancer: correlation with epidermal growth factor receptor mRNA and protein expression and HER-2 status and absence of EGFR-activating mutations. Mod Pathol 18, 1027–1033.PubMedCrossRefGoogle Scholar
  16. 16.
    Loring, P., Cummins, R., O’Grady, A., Kay, E.W. (2005) HER2 positivity in breast carcinoma: a comparison of chromogenic in situ hybridisation with fluorescent in situ hybridisation in tissue microarrays, with targeted evaluation of intratumoural heterogeneity by in situ hybridisation. Appl Immunohistochem Mol Morphol 13, 194–200.PubMedCrossRefGoogle Scholar
  17. 17.
    Kay, E., O’Grady, A., Morgan, J.M., Wozniak, S., and Jasani, B. (2004) Use of tissue microarray for interlaboratory validation of HER2 immunocytochemical and FISH testing. J Clin Pathol 57, 1140–1144.PubMedCrossRefGoogle Scholar
  18. 18.
    Press, M.F., Slamon, D.J., Flom, K.J., Park, J., Zhou, J.Y., and Bernstein, L. (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 Onco 20, 3095–3105.Google Scholar
  19. 19.
    Ricardo, S., Milanezi, F., Carvalho, S., Leitao, D., and Schmitt, F. (2006) HER2 evaluation through the novel rabbit monoclonal antibody SP3 and CISH in tissue microarrays of invasive breast carcinomas. J Clin Pathol 60(9), 1001–1005.PubMedCrossRefGoogle Scholar
  20. 20.
    Sapino, A., Marchio, C., Senetta, R., Castellano, I., Macri, L., Cassoni, P., et al. (2006) Routine assessment of prognostic factors in breast cancer using a multicore tissue microarray procedure. Virchows Arch 449, 288–296.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Royal Cancer Hospital Cancer GeneticsLondonUK
  2. 2.Section of Cancer GeneticsInstitute of Cancer ResearchLondonUK
  3. 3.Laboratory Medicine Skåne, Clinical PathologyUniversity Hospital Malmö, University of LundMalmöSweden

Personalised recommendations

Cite protocol

Buy options