PMID- 21320029 OWN - NLM STAT- MEDLINE DCOM- 20110720 LR - 20161018 IS - 1437-4331 (Electronic) IS - 1434-6621 (Linking) VI - 49 IP - 5 DP - 2011 May TI - Quantification of HER2 autoantibodies in the amplification phenomenon of HER2 in breast cancer. PG - 877-83 LID - 10.1515/CCLM.2011.135 [doi] AB - BACKGROUND: Gene amplification of HER2 (human epidermal growth factor receptor 2) is a well-known phenomenon in various cancers. However, little is known about the mechanism of the gene amplification phenomenon itself. Autoantibodies to cellular receptors have been described in several cancer types. We hypothesised that autoantibodies against HER2 might have a stimulatory capacity and could be the cause of the HER2 gene amplification phenomenon. To investigate this, we developed a test for the detection of autoantibodies against HER2 in serum (S-HER2Ab). METHODS: Blood and tissue samples were collected from 311 women consecutively admitted for surgical treatment of primary breast cancer. Paraffin embedded tissue sections were analysed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). HER2 protein concentrations in tissue were determined in 115 patients. Circulating extracellular domain of HER2 (S-HER2) was measured using the Advia Centaur (Siemens AG, Munich, Germany). Analysis for autoantibodies was developed on an ImmunoCAP 100 (Phadia AB, Uppsala, Sweden) with an automated Fluorescent Enzyme Immuno Assay. RESULTS: Of 311 women, 55 (17.7%) had HER2Ab and 51 (16.4%) showed amplification of the HER2 gene determined by IHC/FISH. Eleven women had detectable S-HER2Ab as well as HER2 gene amplification, but no statistically significant correlation was found between the two phenomena. A significantly higher level of S-HER2Ab was found both in HER2 gene-amplified and non-amplified breast cancer patients compared to an age-matched healthy control group. No statistically significant difference in presence or concentration of S-HER2Ab was found in HER2 gene-amplified vs. non-amplified breast cancer. CONCLUSIONS: S-HER2Ab can be measured accurately with the ImmunoCAP 100. There is an increased prevalence and concentration of S-HER2Ab in breast cancer patients but no correlation with HER2 gene amplification. We conclude that autoantibodies against HER2 do not seem to be the cause of HER2 gene amplification. FAU - Lauterlein, Jens-Jacob L AU - Lauterlein JJ AD - Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark. jejala@dadlnet.dk FAU - Petersen, Eva R B AU - Petersen ER FAU - Olsen, Dorte Aa AU - Olsen DA FAU - Ostergaard, Birthe AU - Ostergaard B FAU - Brandslund, Ivan AU - Brandslund I LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110215 PL - Germany TA - Clin Chem Lab Med JT - Clinical chemistry and laboratory medicine JID - 9806306 RN - 0 (Autoantibodies) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Autoantibodies/*blood/immunology MH - Blood Chemical Analysis/*methods/standards MH - Blotting, Western MH - Breast Neoplasms/blood/*genetics MH - Electrophoresis, Polyacrylamide Gel MH - Female MH - *Gene Amplification MH - Humans MH - Limit of Detection MH - Middle Aged MH - Receptor, ErbB-2/blood/*genetics/immunology MH - Reference Standards MH - Reproducibility of Results EDAT- 2011/02/16 06:00 MHDA- 2011/07/21 06:00 CRDT- 2011/02/16 06:00 PHST- 2011/02/16 06:00 [entrez] PHST- 2011/02/16 06:00 [pubmed] PHST- 2011/07/21 06:00 [medline] AID - 10.1515/CCLM.2011.135 [doi] PST - ppublish SO - Clin Chem Lab Med. 2011 May;49(5):877-83. doi: 10.1515/CCLM.2011.135. Epub 2011 Feb 15.