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Tissue microarrays for high-throughput molecular profiling of tumor specimens

Abstract

Many genes and signalling pathways controlling cell proliferation, death and differentiation, as well as genomic integrity, are involved in cancer development. New techniques, such as serial analysis of gene expression and cDNA microarrays, have enabled measurement of the expression of thousands of genes in a single experiment, revealing many new, potentially important cancer genes1,2. These genome screening tools can comprehensively survey one tumor at a time; however, analysis of hundreds of specimens from patients in different stages of disease is needed to establish the diagnostic, prognostic and therapeutic importance of each of the emerging cancer gene candidates. Here we have developed an array-based high-throughput technique that facilitates gene expression and copy number surveys of very large numbers of tumors. As many as 1000 cylindrical tissue biopsies from individual tumors can be distributed in a single tumor tissue microarray. Sections of the microarray provide targets for parallel in situ detection of DNA, RNA and protein targets in each specimen on the array, and consecutive sections allow the rapid analysis of hundreds of molecular markers in the same set of specimens. Our detection of six gene amplifications as well as p53 and estrogen receptor expression in breast cancer demonstrates the power of this technique for defining new subgroups of tumors.

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References

  1. DeRisi, J. et al. Use of a cDNA microarray to analyse gene expression patterns in human cancer. Nature Genet. 14, 457–460 (1996).

    Article  CAS  Google Scholar 

  2. Zhang, L. et al. Gene expression profiles in normal and cancer cells. Science 276, 1268–1272 (1997).

    Article  CAS  Google Scholar 

  3. Kallioniemi, O.P. et al. ERBB2 amplification in breast cancer analyzed by fluorescence in situ hybridization. Proc. Natl. Acad. Sci. USA. 89, 5321–5325 (1992).

    Article  CAS  Google Scholar 

  4. Ried, T. Interphase cytogenetics and its role in molecular diagnostics of solid tumors. Am. J. Pathol. 152, 325–328 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Pauletti, C., Godolphin, W., Press, M.F. & Slamon, D.J. Detection and quantitation of HER-2/neu gene amplification in human breastcancer archival material using fluorescence in situ hybridization. Oncogene 13, 63–72 (1996).

    CAS  PubMed  Google Scholar 

  6. Slamon, D.J. et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244, 707–712 (1989).

    Article  CAS  Google Scholar 

  7. Barbareschi, M. et al. Cyclin-D1-gene amplification and expression in breast carcinoma: relation with dinicopathologic characteristics and with retinoblastoma gene product, p53 and p21WAF1 immunohistochemical expression. Int. J Cancer 74, 171–174 (1997).

    Article  CAS  Google Scholar 

  8. Persons, D.L., Borelli, K.A. & Hsu, P.H. Quantitation of HER-2/neu and c-myc gene amplification in breast carcinoma using fluorescence in situ hybridization. Mod. Pathol. 10, 720–727 (1997).

    CAS  PubMed  Google Scholar 

  9. Guan, X.Y., Meltzer, P.S., Dalton, W.S. & Trent, J.M. Identification of cryptic sites of DNA sequence amplification in human breast cancer by chromosome microdissection. Nature Genet. 8, 155–161 (1994).

    Article  CAS  Google Scholar 

  10. Muleris, M., Almeida, A., Gerbault-Seureau, M., Malfoy, B. & Dutrillaux, B. Detection of DNA amplification in 17 primary breast carcinomas with homogeneously staining regions by a modified comparative genomic hybridization technique. Genes Chrom. Cancer 10, 160–170 (1994).

    Article  CAS  Google Scholar 

  11. Barlund, M. et al. Increased copy number at 17q22-q24 by CGH in breast cancer is due to high-level amplification of two separate regions. Genes Chrom. Cancer 20, 372–376 (1997).

    Article  CAS  Google Scholar 

  12. Tanner, M.M. et al. Increased copy number at 20q13 in breast cancer: defining the critical region and exclusion of candidate genes. Cancer Res. 54, 4257–4260 (1994).

    CAS  PubMed  Google Scholar 

  13. Noben-Trauth, K. et al. Mybl2 (Bmyb) maps to mouse chromosome 2 and human chromosome 20q13.1. Genomics 35, 610–612 (1996).

    Article  CAS  Google Scholar 

  14. Borg, A. et al. Association of INT2/HST1 coamplification in primary breast cancer with hormone-dependent phenotype and poor prognosis. Br. J. Cancer 63, 136–142 (1991).

    Article  CAS  Google Scholar 

  15. Courjal, F. et al. Mapping of DNA amplifications at 15 chromosomal localizations in 1875 breast tumors: definition of phenotypic groups. Cancer Res. 57, 4360–4367 (1997).

    CAS  PubMed  Google Scholar 

  16. Allred, D.C. et al. Immunocytochemical analysis of estrogen receptors in human breast carcinomas. Evaluation of 130 cases and review of the literature regarding concordance with biochemical assay and clinical relevance. Arch. Surg. 125, 107–113 (1990).

    Article  CAS  Google Scholar 

  17. Molino, A. et al. Prognostic significance of estrogen receptors in 405 primary breast cancers: a comparison of immunohistochemical and biochemical methods. Breast Cancer Res. Treat. 45, 241–249 (1997).

    Article  CAS  Google Scholar 

  18. Battifora, H. The multitumor (sausage) tissue block: novel method for immunohistochemical antibody testing. Lab. Invest. 55, 244–248 (1986).

    CAS  PubMed  Google Scholar 

  19. Battifora, H. & Mehta, P. The checkerboard tissue block. An improved multitissue control block. Lab. Invest. 63, 722–724 (1990).

    CAS  PubMed  Google Scholar 

  20. Press, M.F., Hung, G., Godolphin, W. & Slamon, D.J. Sensitivity of HER-2/neu antibodies in archival tissue samples: potentialsource of error in immunohistochemical studies of oncogene expression. Cancer Res. 54, 2771–2777 (1994).

    CAS  PubMed  Google Scholar 

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Kononen, J., Bubendorf, L., Kallionimeni, A. et al. Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 4, 844–847 (1998). https://doi.org/10.1038/nm0798-844

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