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Specific antibodies and sensitive immunoassays for the human epidermal growth factor receptors (HER2, HER3, and HER4).

Abstract The use of trastuzumab in patients with breast cancer that overexpresses human epidermal growth factor receptor 2 has significantly improved treatment outcomes. However, a substantial proportion of this patient group still experiences progression of the disease after receiving the drug. Evaluation of the changes in expression of the human epidermal growth factor receptors could be of interest. Monoclonal antibodies against the extracellular domain of the human growth factor receptors, 2, 3, and 4, have been raised, and specific and sensitive immunoassays have been established. Sera from healthy individuals (Nordic Reference Interval Project and Database) were analyzed in the human epidermal growth factor receptor 2 assay (N = 805) and the human epidermal growth factor receptor 3 and 4 assays (N = 114), and reference limits were calculated. In addition, sera from 208 individual patients with breast cancer were tested in all three assays. Finally, the human epidermal growth factor receptor 2 assay was compared with a chemiluminescent immunoassay for serum human epidermal growth factor receptor 2/neu. Reference values were as follows: human epidermal growth factor receptor 2, <2.5 µg/L; human epidermal growth factor receptor 3, <2.8 µg/L; and human epidermal growth factor receptor 4, <1.8 µg/L. There were significant differences in human epidermal growth factor receptor 2 and human epidermal growth factor receptor 3 serum levels between the patients with tissue human epidermal growth factor receptor 2-positive and tissue human epidermal growth factor receptor 2-negative ( p = 0.0026, p = 0.000011) tumors, but not in the serum levels of human epidermal growth factor receptor 4 ( p = 0.054). There was good agreement between the in-house human epidermal growth factor receptor 2 assay and the chemiluminescent immunoassay. Our new specific antibodies for all the three human epidermal growth factor receptors may prove valuable in the development of novel anti-human epidermal growth factor receptor targeted therapies with sensitive immunoassays for measuring serum levels of the respective targets and in monitoring established treatment.
PMID
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Authors

Mayor MeshTerms
Keywords

Growth factor receptor and biomarker

Journal Title tumour biology : the journal of the international society for oncodevelopmental biology and medicine
Publication Year Start




PMID- 28653892
OWN - NLM
STAT- MEDLINE
DA  - 20170627
DCOM- 20170711
LR  - 20170713
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 39
IP  - 6
DP  - 2017 Jun
TI  - Specific antibodies and sensitive immunoassays for the human epidermal growth
      factor receptors (HER2, HER3, and HER4).
PG  - 1010428317707436
LID - 10.1177/1010428317707436 [doi]
AB  - The use of trastuzumab in patients with breast cancer that overexpresses human
      epidermal growth factor receptor 2 has significantly improved treatment outcomes.
      However, a substantial proportion of this patient group still experiences
      progression of the disease after receiving the drug. Evaluation of the changes in
      expression of the human epidermal growth factor receptors could be of interest.
      Monoclonal antibodies against the extracellular domain of the human growth factor
      receptors, 2, 3, and 4, have been raised, and specific and sensitive immunoassays
      have been established. Sera from healthy individuals (Nordic Reference Interval
      Project and Database) were analyzed in the human epidermal growth factor receptor
      2 assay (N = 805) and the human epidermal growth factor receptor 3 and 4 assays
      (N = 114), and reference limits were calculated. In addition, sera from 208
      individual patients with breast cancer were tested in all three assays. Finally, 
      the human epidermal growth factor receptor 2 assay was compared with a
      chemiluminescent immunoassay for serum human epidermal growth factor receptor
      2/neu. Reference values were as follows: human epidermal growth factor receptor
      2, &lt;2.5 microg/L; human epidermal growth factor receptor 3, &lt;2.8 microg/L; and
      human epidermal growth factor receptor 4, &lt;1.8 microg/L. There were significant
      differences in human epidermal growth factor receptor 2 and human epidermal
      growth factor receptor 3 serum levels between the patients with tissue human
      epidermal growth factor receptor 2-positive and tissue human epidermal growth
      factor receptor 2-negative ( p = 0.0026, p = 0.000011) tumors, but not in the
      serum levels of human epidermal growth factor receptor 4 ( p = 0.054). There was 
      good agreement between the in-house human epidermal growth factor receptor 2
      assay and the chemiluminescent immunoassay. Our new specific antibodies for all
      the three human epidermal growth factor receptors may prove valuable in the
      development of novel anti-human epidermal growth factor receptor targeted
      therapies with sensitive immunoassays for measuring serum levels of the
      respective targets and in monitoring established treatment.
FAU - Broughton, Marianne Nordlund
AU  - Broughton MN
AD  - 1 Department of Medical Biochemistry, Radiumhospitalet, Oslo University Hospital,
      Oslo, Norway.
FAU - Westgaard, Arne
AU  - Westgaard A
AD  - 2 Department of Oncology, Radiumhospitalet, Oslo University Hospital, Oslo,
      Norway.
FAU - Paus, Elisabeth
AU  - Paus E
AD  - 1 Department of Medical Biochemistry, Radiumhospitalet, Oslo University Hospital,
      Oslo, Norway.
FAU - Oijordsbakken, Miriam
AU  - Oijordsbakken M
AD  - 1 Department of Medical Biochemistry, Radiumhospitalet, Oslo University Hospital,
      Oslo, Norway.
FAU - Henanger, Karoline J
AU  - Henanger KJ
AD  - 1 Department of Medical Biochemistry, Radiumhospitalet, Oslo University Hospital,
      Oslo, Norway.
FAU - Naume, Bjorn
AU  - Naume B
AD  - 2 Department of Oncology, Radiumhospitalet, Oslo University Hospital, Oslo,
      Norway.
AD  - 3 Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, 
      Norway.
FAU - Bjoro, Trine
AU  - Bjoro T
AD  - 1 Department of Medical Biochemistry, Radiumhospitalet, Oslo University Hospital,
      Oslo, Norway.
AD  - 3 Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, 
      Norway.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental
      Biology and Medicine
JID - 8409922
RN  - 0 (Antibodies, Monoclonal)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (ERBB3 protein, human)
RN  - EC 2.7.10.1 (ERBB4 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 2.7.10.1 (Receptor, ErbB-3)
RN  - EC 2.7.10.1 (Receptor, ErbB-4)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Antibodies, Monoclonal/immunology
MH  - Antibody Specificity/immunology
MH  - Breast Neoplasms/*blood/drug therapy/immunology/pathology
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Hypersensitivity/genetics
MH  - Immunoassay
MH  - Receptor, ErbB-2/*blood/immunology
MH  - Receptor, ErbB-3/*blood/immunology
MH  - Receptor, ErbB-4/*blood/genetics/immunology
MH  - Trastuzumab/administration &amp; dosage
OTO - NOTNLM
OT  - Growth factor receptor and biomarker
EDAT- 2017/06/28 06:00
MHDA- 2017/07/14 06:00
CRDT- 2017/06/28 06:00
AID - 10.1177/1010428317707436 [doi]
PST - ppublish
SO  - Tumour Biol. 2017 Jun;39(6):1010428317707436. doi: 10.1177/1010428317707436.