title: Her-2/neu overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic significance and comparative analysis in primary and metastatic tumors.
abstract: OBJECTIVE
  The prognostic significance of Her-2/neu overexpression in muscle-invasive urothelial carcinoma of the bladder is largely unknown. Accurate determination of Her-2/neu overexpression may have therapeutic importance.
  
  
  METHODS
  Eighty consecutive cases of muscle-invasive urothelial carcinoma of the bladder treated by radical cystectomy with available follow-up were analyzed. In each case, one representative section was stained with anti-Her-2/neu. Staining was graded as 1 = faint/equivocal, 2 = moderate, and 3 = strong and was considered positive if > or =2. In those cases with a metastasis, the stain was also performed in the metastatic tumor. Results were correlated with survival.
  
  
  RESULTS
  Twenty-two (28%) cases were considered Her-2/neu-positive in the primary tumor, and 17 of 32 (53%) were considered Her-2/neu-positive in the lymph node metastasis. Median survival for Her-2/neu-positive primary tumors was 33 months, compared with 50 months for Her-2/neu-negative cases (P = 0.46). Similarly, Her-2/neu overexpression in the lymph node metastasis did not predict survival. Sixty metastatic urothelial carcinomas were further studied by comparing Her-2/neu expression in the primary tumor with that of the lymph node and/or distant metastasis. Forty-five percent of Her-2/neu-negative primary tumors had a Her-2/neu-positive lymph node metastasis, whereas only one case (8%) of Her-2/neu-positive primary tumors was Her-2/neu-negative in the lymph node metastasis (P = 0.009). Similarly, 67% of Her-2/neu-negative primary tumors had a Her-2/neu-positive distant metastasis, whereas no Her-2/neu-positive primary tumor was negative in the metastasis (P = 0.429).
  
  
  CONCLUSIONS
  Her-2/neu overexpression in primary or metastatic tumor did not predict survival in this cohort of muscle-invasive tumors. Overexpression in the primary tumors consistently predicts overexpression in a distant or regional metastasis. However, some Her-2/neu-negative primary tumors may show overexpression in their corresponding metastasis. Her-2/neu analysis in a metastasis may be necessary to accurately determine Her-2/neu status in metastatic bladder urothelial carcinoma.
authors.affiliation: Department of Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Jimenez
authors.forename: M
authors.initials: M
authors.lastname: Hussain
authors.forename: F J
authors.initials: FJ
authors.lastname: Bianco
authors.forename: U
authors.initials: U
authors.lastname: Vaishampayan
authors.forename: P
authors.initials: P
authors.lastname: Tabazcka
authors.forename: W A
authors.initials: WA
authors.lastname: Sakr
authors.forename: J E
authors.initials: JE
authors.lastname: Pontes
authors.forename: D P
authors.initials: DP
authors.lastname: Wood
authors.forename: D J
authors.initials: DJ
authors.lastname: Grignon
mesh_terms: D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D009132:Muscles / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology*; D019459:Urothelium / Q000737:chemistry / Q000473:pathology*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases