title: HER-2/neu protein overexpression and gene amplification in human transitional cell carcinoma of the bladder.
abstract: OBJECTIVE
  To assess HER-2/neu gene status by fluorescence in situ hybridization and protein expression by immunohistochemistry in human bladder transitional cell carcinoma (TCC). In breast carcinoma, HER-2/neu gene amplification and receptor protein overexpression are tightly correlated and have prognostic and therapeutic implications.
  
  
  METHODS
  We used 54 randomly selected TCC specimens obtained from 1998 to 2000. Each specimen was fixated in 10% neutral-buffered formalin and embedded in paraffin. Of the 54 specimens, 7 were grade 1 (13%), 26 were grade 2 (48%), and 21 were grade 3 (39%); 36 (67%) were superficial (Stage Ta or T1) and 18 (33%) were invasive (Stage T2 or T3). The specimens were analyzed for HER-2/neu protein overexpression by immunohistochemistry and for gene amplification using fluorescence in situ hybridization.
  
  
  RESULTS
  Of the 54 specimens, 14 (26%) were positive for protein overexpression. One (14%) of the 7 grade 1 tumors was positive for protein overexpression, 3 (12%) of 26 grade 2 tumors were positive, and 10 (48%) of 21 grade 3 tumors were positive (P = 0.0195). Six (17%) of 36 Stage Ta or T1 specimens and 8 (44%) of 18 Stage T2 or T3 specimens were positive for protein overexpression (P = 0.01). None of the 54 TCC specimens showed amplification of the HER-2/neu gene using fluorescence in situ hybridization.
  
  
  CONCLUSIONS
  HER-2/neu protein overexpression is present in human bladder TCC, with a statistically significant increase in overexpression in grade 3, and invasive specimens. Gene amplification does not appear to be the mechanism of protein overexpression. The prognostic significance of these findings and the application of HER-2/neu in treatment needs additional investigation.
authors.affiliation: Department of Urology, Rush Medical College, Chicago, Illinois, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Coogan
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Estrada
authors.forename: Shiv
authors.initials: S
authors.lastname: Kapur
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Bloom
mesh_terms: D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005784:Gene Amplification / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases