title: HER-2/neu is overexpressed infrequently in patients with prostate carcinoma. Results from the California Cancer Consortium Screening Trial.
abstract: BACKGROUND
  The overexpression of HER-2/neu is found in 20-30% of patients with breast carcinoma and is an adverse prognostic factor. HER-2 overexpression also has been reported in up to 60% of patients with hormone-refractory prostate carcinoma (HRPC) and was correlated with shortened survival. Trastuzumab (Herceptin) is a humanized monoclonal antibody that binds to the HER-2 receptor and has antitumor activity in patients with HER-2-overexpressing breast carcinoma. The authors report the results of HER-2 screening from a Phase II trial of chemotherapy with trastuzumab and docetaxel in patients with HER-2-overexpressing prostate carcinoma.
  
  
  METHODS
  Archival paraffin embedded tumor tissue was obtained from potentially eligible patients and was screened for HER-2 expression by immunohistochemistry (IHC) using a specialized test kit. Shed HER-2 antigen in serum also was determined using an enzyme-linked immunosorbent assay (ELISA). HER-2 gene amplification was assessed by fluorescent in situ hybridization (FISH). Patients with IHC scores of 2+ or 3+ were considered to have HER-2 overexpression and were eligible for the trial. To date, 62 patients with HRPC have been screened.
  
  
  RESULTS
  The median patient age was 72 years, and Gleason scores were < 5 in 1 patients, 5-7 in 24 patients, > 7 in 23 patients, and not specified in 14 patients. IHC HER-2 expression was 0 in 28 patients, 1+ in 14 patients, 2+ in 4 patients, and 3+ in 1 patients. Fifteen patients had either suboptimal tissue (13 patients) for interpretation or had pending results (2 patients). Therefore, 8% of all patients screened (5 of 62 patients) had HER-2 overexpression by IHC. Quantitative ELISA for shed HER-2 was available in 32 patients; this level was elevated (> 15 ng/mL) in only 2 patients, and neither had HER-2 expression by IHC. Of the 5 patients with 2+ or 3+ HER-2 expression by IHC, none had elevated shed HER-2 antigen levels by ELISA. FISH for HER-2 amplification was performed on 12 specimens; 5 of these specimens were uninterpretable due to specimen artifact, and none of the remaining 7 specimens had HER-2 amplification, defined as a ratio > 1. Patient age and Gleason score were not correlated with HER-2 status.
  
  
  CONCLUSIONS
  Unlike breast carcinoma and contrary to prior reports, HER-2 overexpression by IHC in archival prostate tissue from patients who eventually developed hormone-refractory disease was infrequent. There did not appear to be any correlation between HER-2 overexpression by IHC and shed HER-2 antigen levels in serum by ELISA in this tumor type. Whether trastuzumab possesses single-agent activity or modulates chemotherapy response in tumor types other than breast carcinoma remains to be determined.
authors.affiliation: University of California Davis Cancer Center, Division of Hematology-Oncology, 4501 X Street, Sacramento, CA 95817, USA. primo.lara@ucdmc.ucdavis.edu
authors.forename: Primo N
authors.initials: PN
authors.lastname: Lara
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Meyers
authors.forename: Carl R
authors.initials: CR
authors.lastname: Gray
authors.forename: Regina Gandour
authors.initials: RG
authors.lastname: Edwards
authors.forename: Paul H
authors.initials: PH
authors.lastname: Gumerlock
authors.forename: Caren
authors.initials: C
authors.lastname: Kauderer
authors.forename: Garrett
authors.initials: G
authors.lastname: Tichauer
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Twardowski
authors.forename: James H
authors.initials: JH
authors.lastname: Doroshow
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases