PMID- 23089711
OWN - NLM
STAT- MEDLINE
DCOM- 20130318
LR  - 20181202
IS  - 1437-4331 (Electronic)
IS  - 1434-6621 (Linking)
VI  - 50
IP  - 10
DP  - 2012 Oct 1
TI  - Increased concentrations of growth factors and activation of the EGFR system in 
      breast cancer.
PG  - 1809-18
LID - /j/cclm.2012.50.issue-10/cclm-2011-0823/cclm-2011-0823.xml [pii]
LID - 10.1515/cclm-2011-0823 [doi]
AB  - 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-alpha (TGFalpha), 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, TGFalpha and 
      AREG were upregulated in cancer tissue as compared with autologous reference 
      tissue while EGFR, pEGFR and EGF were downregulated (p<10-6). 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<10-6). HB-EGF in cancer tissue was positively associated with 
      high grade tumors (p<10-6) 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.
FAU - Olsen, Dorte Aa
AU  - Olsen DA
AD  - Department of Clinical Biochemistry, Vejle Hospital, Vejle, Denmark. 
      Dorte.Aalund.Olsen@slb.regionsyddanmark.dk
FAU - Bechmann, Troels
AU  - Bechmann T
FAU - Ostergaard, Birthe
AU  - Ostergaard B
FAU - Wamberg, Peter A
AU  - Wamberg PA
FAU - Jakobsen, Erik H
AU  - Jakobsen EH
FAU - Brandslund, Ivan
AU  - Brandslund I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Clin Chem Lab Med
JT  - Clinical chemistry and laboratory medicine
JID - 9806306
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Ligands)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Breast/metabolism/pathology
MH  - Breast Neoplasms/*metabolism/pathology
MH  - ErbB Receptors/*metabolism
MH  - Female
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/*metabolism
MH  - Ligands
MH  - Middle Aged
MH  - Phosphorylation
MH  - Receptor, ErbB-2/*metabolism
EDAT- 2012/10/24 06:00
MHDA- 2013/03/19 06:00
CRDT- 2012/10/24 06:00
PHST- 2011/11/08 00:00 [received]
PHST- 2012/04/02 00:00 [accepted]
PHST- 2012/10/24 06:00 [entrez]
PHST- 2012/10/24 06:00 [pubmed]
PHST- 2013/03/19 06:00 [medline]
AID - /j/cclm.2012.50.issue-10/cclm-2011-0823/cclm-2011-0823.xml [pii]
AID - 10.1515/cclm-2011-0823 [doi]
PST - ppublish
SO  - Clin Chem Lab Med. 2012 Oct 1;50(10):1809-18. doi: 10.1515/cclm-2011-0823.