title: Identification of the coexisting HER2 gene amplification and novel mutations in the HER2 protein-overexpressed mucinous epithelial ovarian cancer.
abstract: BACKGROUND
  Although overexpression, amplification, and somatic mutation of the HER2 gene have been noted in various types of human cancers, we report here for the first time that novel mutations and amplification of the HER2 gene occurred concomitantly in mucinous epithelial ovarian cancer (EOC).
  
  
  METHODS
  Twenty-seven tissue microarray samples from EOC patients were analyzed by immunohistochemistry (IHC) with Dako c-erb-B2 antibody and subsequently were examined by fluorescence in situ hybridization (FISH) with the Abbott PathVysion HER2 DNA Probe Kit. HER2 gene, exon 18-24, encoding a tyrosine kinase domain, was analyzed by polymerase chain reaction (PCR) and direct sequencing.
  
  
  RESULTS
  The FISH-IHC paired results confirmed 19 concordant negative results and 3 concordant positive results. Moreover, all 4 HER2-amplified cases were of the mucinous type, whereas the remaining 23 HER2-nonamplified cases were of the nonmucinous type. The 4 mucinous EOC cases with HER2 gene amplification were selected and further analyzed for HER2 gene mutations. Data revealed that somatic mutations were present in 2 cases (R970W and E971G), but absent in the other 2 cases.
  
  
  CONCLUSIONS
  HER2 protein overexpression correlated significantly with HER2 gene amplification in EOC (P = 0.027). It is surprising that all 4 cases of mucinous EOC showed HER2 gene amplification confirmed by FISH testing. However, we suppose that increasing the number of cases would possibly modify the results. This study also showed that both HER2 gene amplification and somatic mutations are not mutually exclusive in mucinous EOC. Further studies are warranted to investigate the potential role of anti-HER2 therapy.
authors.affiliation: Department of Pathology, Chung-Shan Medical University Hospital and School of Medicine, Chung-Shan Medical University, Taichung, Taiwan.
authors.forename: Wea-Lung
authors.initials: WL
authors.lastname: Lin
authors.forename: Wu-Hsien
authors.initials: WH
authors.lastname: Kuo
authors.forename: Fong-Lin
authors.initials: FL
authors.lastname: Chen
authors.forename: Ming-Yung
authors.initials: MY
authors.lastname: Lee
authors.forename: Alexandra
authors.initials: A
authors.lastname: Ruan
authors.forename: Yeu-Sheng
authors.initials: YS
authors.lastname: Tyan
authors.forename: Jeng-Dong
authors.initials: JD
authors.lastname: Hsu
authors.forename: Hung
authors.initials: H
authors.lastname: Chiang
authors.forename: Chih-Ping
authors.initials: CP
authors.lastname: Han
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D009154:Mutation / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D004273:DNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human