Early Detection and Diagnosis

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Implementation of a novel microarray-based diagnostic test for cancer of unknown primary

  1. Ryan K. van Laar1,†,§,
  2. Xiao-Jun Ma2,§,
  3. Daphne de Jong3,
  4. Diederik Wehkamp1,
  5. Arno N. Floore1,
  6. Marc O. Warmoes1,‡,
  7. Iris Simon1,
  8. Wilson Wang2,
  9. Mark Erlander2,
  10. Laura J. van't Veer1,3,
  11. Annuska M. Glas1,¶,*

Article first published online: 14 APR 2009

DOI: 10.1002/ijc.24504

Issue

International Journal of Cancer

International Journal of Cancer

Volume 125, Issue 6, pages 1390–1397, 15 September 2009

Additional Information

How to Cite

van Laar, R. K., Ma, X.-J., de Jong, D., Wehkamp, D., Floore, A. N., Warmoes, M. O., Simon, I., Wang, W., Erlander, M., van't Veer, L. J. and Glas, A. M. (2009), Implementation of a novel microarray-based diagnostic test for cancer of unknown primary. Int. J. Cancer, 125: 1390–1397. doi: 10.1002/ijc.24504

Author Information

  1. 1

    Agendia BV, SciencePark 406, 1098 XH Amsterdam, The Netherlands

  2. 2

    BioTheranostics, San Diego, CA

  3. 3

    Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

  1. †

    Regeneron Pharmaceuticals Inc, Tarrytown, NY

  2. ‡

    VU University Medical Center, Amsterdam, The Netherlands

  1. §

    The first two authors contributed equally to this work.

  2. Fax: +31204621505.

*Agendia BV, SciencePark 406, 1098 XH Amsterdam, The Netherlands

  1. §

    The first two authors contributed equally to this work.

  2. Fax: +31204621505.

Publication History

  1. Issue published online: 14 JUL 2009
  2. Article first published online: 14 APR 2009
  3. Manuscript Accepted: 20 MAR 2009
  4. Manuscript Received: 27 AUG 2008

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Keywords:

  • cancer of unknown primary;
  • microarray;
  • molecular diagnostics;
  • gene expression profiling;
  • tumor of unknown origin

Abstract

Patients with carcinoma of unknown primary (CUP) present with metastatic disease for which the primary site cannot be found, despite extensive standard investigation. Here, we describe the development and implementation of the first clinically available microarray-based test for this cancer type (CUPPrint), based on 633 individual tumors representing 30 carcinoma and 17 noncarcinoma classes. Tissue of origin prediction for either fresh frozen or paraffin-embedded tumor samples is achieved with the use of a custom 8-pack 1.9k microarray and robust classification algorithm. An expression profile of 495 genes was used to predict tumor origin by applying a k-nearest neighbor algorithm. Internal cross-validation and analysis of an independent, previously published, 229-sample dataset revealed that clinically informative predictions were made for up to 94% of samples analyzed. Analysis of 13 previously published CUP specimens yielded predicted tumor origins that supported the clinical suspicion in 12 cases (92%). Microarray profiling presents a promising tool to assist in the identification of the primary tumor and might direct a more tailored treatment for CUP patients. © 2009 UICC

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