Breast Cancer Research and Treatment

, Volume 120, Issue 3, pp 567–579

Data driven derivation of cutoffs from a pool of 3,030 Affymetrix arrays to stratify distinct clinical types of breast cancer

  • Thomas Karn
  • Dirk Metzler
  • Eugen Ruckhäberle
  • Lars Hanker
  • Regine Gätje
  • Christine Solbach
  • Andre Ahr
  • Marcus Schmidt
  • Uwe Holtrich
  • Manfred Kaufmann
  • Achim Rody
Preclinical study

Abstract

Pooling of microarray datasets seems to be a reasonable approach to increase sample size when a heterogeneous disease like breast cancer is concerned. Different methods for the adaption of datasets have been used in the literature. We have analyzed influences of these strategies using a pool of 3,030 Affymetrix U133A microarrays from breast cancer samples. We present data on the resulting concordance with biochemical assays of well known parameters and highlight critical pitfalls. We further propose a method for the inference of cutoff values directly from the data without prior knowledge of the true result. The cutoffs derived by this method displayed high specificity and sensitivity. Markers with a bimodal distribution like ER, PgR, and HER2 discriminate different biological subtypes of disease with distinct clinical courses. In contrast, markers displaying a continuous distribution like proliferation markers as Ki67 rather describe the composition of the mixture of cells in the tumor.

Keywords

Breast cancer Microarray Cutoff Distribution Pooling Meta-analysis Bimodal markers 

Supplementary material

10549_2009_416_MOESM1_ESM.pdf (428 kb)
Supplementary material 1 (PDF 429 kb)

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Thomas Karn
    • 1
  • Dirk Metzler
    • 2
  • Eugen Ruckhäberle
    • 1
  • Lars Hanker
    • 1
  • Regine Gätje
    • 1
  • Christine Solbach
    • 1
  • Andre Ahr
    • 1
  • Marcus Schmidt
    • 3
  • Uwe Holtrich
    • 1
  • Manfred Kaufmann
    • 1
  • Achim Rody
    • 1
  1. 1.Department of Obstetrics and GynecologyJ. W. Goethe UniversityFrankfurtGermany
  2. 2.Department of Biology IILudwig-Maximilians-UniversityMunichGermany
  3. 3.Department of Obstetrics and GynecologyJohannes Gutenberg UniversityMainzGermany

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