Breast Cancer Research and Treatment

, Volume 122, Issue 1, pp 105–110 | Cite as

The complete family of epidermal growth factor receptors and their ligands are co-ordinately expressed in breast cancer

  • Emmet McIntyre
  • Edith Blackburn
  • Philip J. Brown
  • Colin G. Johnson
  • William J. GullickEmail author
Preclinical study


The levels of expression of the four receptors and eleven ligands composing the epidermal growth factor family were measured using immunohistochemical staining in one hundred cases of breast cancer. All of the family were expressed to some degree in some cases; however, individual cases showed a very wide range of expression of the family from essentially none to all the factors at high levels. The highest aggregate level of expression of a receptor was HER2 followed by HER1, then HER3, then HER4. The ligands (including two splice variants of the NRG1 and NRG2 genes) broadly fell into three groups, those with the highest aggregate expression were Epigen, Epiregulin, Neuregulin 1α, Neuregulin 2α, Neuregulin 2β, Neuregulin 4 and TGFα, moderate expression was seen with EGF, Neuregulin 1β and Neuregulin 3, and relatively low levels of expression were seen of HB-EGF, Betacellulin and Amphiregulin. Statistical analysis using Spearman’s Rank Correlation showed a positive correlation of expression between each of the factors. Analysing the data using the Cox Proportional Hazards model showed that, in this dataset, the most powerful predictors of relapse free interval and overall survival were the combined measurement of only Epigen and Neuregulin 4.


ErbB Growth factor Growth factor receptor Prognosis Breast cancer 



We are grateful to Professor Adrian Harris and Dr Russell Leek for the tissue array samples. Edith Blackburn is supported by a grant from the E. B. Hutchinson Trust.

Supplementary material

10549_2009_536_MOESM1_ESM.pdf (43 kb)
Supplementary material 1 (PDF 42 kb)


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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Emmet McIntyre
    • 1
  • Edith Blackburn
    • 2
  • Philip J. Brown
    • 3
  • Colin G. Johnson
    • 1
  • William J. Gullick
    • 2
    Email author
  1. 1.Computing LaboratoryUniversity of KentCanterburyUK
  2. 2.Department of BiosciencesUniversity of KentCanterburyUK
  3. 3.Institute of Mathematics, Statistics and Actuarial ScienceUniversity of KentCanterburyUK

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