Annals of Oncology Advance Access published online on October 24, 2007
Annals of Oncology, doi:10.1093/annonc/mdm431
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© 2007 European Society for Medical Oncology
ErbB/HER ligands in human breast cancer, and relationships with their receptors, the bio-pathological features and prognosis
1 Laboratoire d'Oncologie Moléculaire Humaine
2 Département de Sénologie, Centre Oscar Lambret, Lille Cedex, France
* Correspondence to: Dr F. Révillion, Laboratoire d'Oncologie Moléculaire Humaine, Centre Oscar Lambret, BP 307, 59020 Lille Cedex, France. Tel: +33-3-20-29-59-59; Fax: +33-3-20-29-59-62; E-mail: f-revillion{at}o-lambret.fr
Background: The aim of this study is to provide an expression profile of ErbB/HER ligands in breast cancer. We analysed the relationships with their receptors, the bio-pathological features and prognosis.
Patients and methods: Epidermal growth factor (EGF), transforming growth factor-
(TGF), amphiregulin (AREG), betacellulin (BTC), heparin-binding EGF-like growth factor (HB-EGF), epiregulin (EREG) and neuregulins1–4 (NRG1–4) were quantified in 363 tumours by real-time reverse transcription–polymerase chain reaction using TaqMan probes.
Results: Ligands were detected in 80%–96% of the cases, except NRG3 (42%) and EREG (45.5%). At least one ligand was expressed in 304 cases (cut-off: upper quartile). Almost all combinations of receptor and ligand co-expressions were observed, but TGF is preferentially expressed in tumours co-expressing EGFR/HER3, NRG3 in those co-expressing EGFR/HER4, AREG and EREG in those co-expressing HER2/HER4. EGF and AREG were associated with estradiol receptors, small tumour size, low histoprognostic grading, high HER4 levels. TGF, HB-EGF and NRG2 were negatively related to these parameters. In Cox univariate analyses, EGF was a prognostic factor.
Conclusion: Our study demonstrates that (i) ErbB/HER ligands, including BTC and EREG, are expressed in most breast cancers; and (ii) TGF, HB-EGF and NRG2 high expressions are related to the biological aggressiveness of the tumours.
breast cancer, EGF-related ligands, ErbB/HER receptors, expression profile, prognosis
Received for publication January 30, 2007. Revision received June 30, 2007. Accepted for publication July 26, 2007.
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