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Increased concentrations of growth factors and activation of the EGFR system in breast cancer.
- Source :
- Clinical Chemistry & Laboratory Medicine; Oct2012, Vol. 50 Issue 10, p1809-1818, 10p, 3 Charts, 5 Graphs
- Publication Year :
- 2012
-
Abstract
- Background: In this study the total and phosphorylated amount of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) were measured together with EGFR ligands in tissue samples of breast cancer patients in order to investigate interrelations and possible prognostic values. Methods: Samples of malignant and non-cancer autologous reference tissue were collected from 415 breast cancer patients. The tissue samples were cut and either paraffin-embedded or homogenized in a lysis buffer to extract the proteins. HER2 was measured using both immunohistochemistry (IHC)/fluorescence in situ hybridization (FISH) and ADVIA Centaur. Phosphorylated HER2 and EGFR (pHER2, pEGFR), total EGFR and the ligands: epidermal growth factor (EGF), transforming growth factor-α (TGFα), amphiregulin (AREG), heparin-binding EGF-like growth factor (HB-EGF), betacellulin (BTC) and epiregulin (EREG) were measured using the Luminex. Results: The HER2 positivity rate was determined to be 25.2% by the Centaur method vs. 15.8% by IHC and FISH. HER2, HB-EGF, TGFα and AREG were upregulated in cancer tissue as compared with autologous reference tissue while EGFR, pEGFR and EGF were downregulated (p<10<superscript>-6</superscript>). pEGFR in autologous reference tissue was negatively correlated to the number of positive lymph nodes and to the tumor size (p=0.0007 and p=0.001, respectively) and furthermore, decreased in the group of mastectomy operated patients as compared with the lumpectomy group (p<10<superscript>-6</superscript>). HB-EGF in cancer tissue was positively associated with high grade tumors (p<10<superscript>-6</superscript>) and pHER2, HB-EGF and BTC were associated with poor disease free survival (p=0.017, p=0.012 and p=0.0026, respectively). Conclusions: Our study demonstrated a profound activation of the EGFR system. HB-EGF was increased by factor 10 in cancer tissue and related to the biological aggressiveness of the tumors, and pHER2, HB-EGF and BTC were associated with poor clinical outcome. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14346621
- Volume :
- 50
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- Clinical Chemistry & Laboratory Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 83468948
- Full Text :
- https://doi.org/10.1515/cclm-2011-0823