title: HER2 overexpression and amplification is present in a subset of ovarian mucinous carcinomas and can be targeted with trastuzumab therapy.
abstract: BACKGROUND
  The response rate of ovarian mucinous carcinomas to paclitaxel/carboplatin is low, prompting interest in targeted molecular therapies. We investigated HER2 expression and amplification, and the potential for trastuzumab therapy in this histologic subtype of ovarian cancer.
  
  
  METHODS
  HER2 status was tested in 33 mucinous carcinomas and 16 mucinous borderline ovarian tumors (BOT)). Five cases with documented recurrence and with tissue from the recurrence available for testing were analyzed to determine whether HER2 amplification status changed over time. Three prospectively identified recurrent mucinous ovarian carcinomas were assessed for HER2 amplification and patients received trastuzumab therapy with conventional chemotherapy.
  
  
  RESULTS
  Amplification of HER2 was observed in 6/33 (18.2%) mucinous carcinomas and 3/16 (18.8%) BOT. HER2 amplification in primary mucinous carcinomas was not associated with an increased likelihood of recurrence. The prospectively identified recurrent mucinous carcinomas showed overexpression and amplification of HER2; one patient's tumor responded dramatically to trastuzumab in combination with conventional chemotherapy, while another patient experienced an isolated central nervous system recurrence after trastuzumab therapy.
  
  
  CONCLUSIONS
  HER2 amplification is relatively common in ovarian mucinous carcinomas (6/33, 18.2%), although not of prognostic significance. Trastuzumab therapy is a treatment option for patients with mucinous carcinoma when the tumor has HER2 amplification and overexpression.
authors.affiliation: Department of Gynaecology and Obstetrics, University of British Columbia, Vancouver, BC, Canada. jessica.mcalpine@vch.ca
authors.forename: Jessica N
authors.initials: JN
authors.lastname: McAlpine
authors.forename: Kimberly C
authors.initials: KC
authors.lastname: Wiegand
authors.forename: Russell
authors.initials: R
authors.lastname: Vang
authors.forename: Bridgett M
authors.initials: BM
authors.lastname: Ronnett
authors.forename: Anna
authors.initials: A
authors.lastname: Adamiak
authors.forename: Martin
authors.initials: M
authors.lastname: Köbel
authors.forename: Steve E
authors.initials: SE
authors.lastname: Kalloger
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Swenerton
authors.forename: David G
authors.initials: DG
authors.lastname: Huntsman
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
authors.forename: Dianne M
authors.initials: DM
authors.lastname: Miller
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000145:classification / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016503:Drug Delivery Systems; D005260:Female; D005784:Gene Amplification / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000145:classification / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D012008:Recurrence; D012189:Retrospective Studies; D000068878:Trastuzumab; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068878:Trastuzumab