title: Human epidermal growth factor receptor 2 expression status provides independent prognostic information in patients with urothelial carcinoma of the urinary bladder.
abstract: OBJECTIVE
  to test whether the expression of human epidermal growth factor receptor 2 (HER-2) is of prognostic value in a contemporary cohort of patients with urothelial carcinoma of the urinary bladder (UCB).
  
  
  METHODS
  tissue microarrays of 198 patients were constructed and immunohistochemical stainings were performed on the primary tumours and on lymphatic nodal metastases. All patients were treated with radical cystectomy (RC) and regional lymphadenectomy for UCB. HER-2 expression was assessed using continuous HER-2 expression scores (ranging from 0.1 to 3.9) generated using an automated cellular imaging system. Scores of ≥ 1.0 in at least 10% of tumour cells were regarded as HER-2 positive. We correlated HER-2 scores with pathological and clinical variables, including disease recurrence and cancer-specific mortality.
  
  
  RESULTS
  of 198 patients undergoing RC with lymphadenectomy, there was HER-2 positivity in 55 primary tumours (27.8%) compared with 44.2% of the evaluable positive lymph nodes (P < 0.001). HER-2 positivity was significantly associated with the presence of lymphovascular invasion (LVI; P= 0.026). With a median (range) follow-up of 35.4 (1.3-176.1) months, 101 patients (51.0%) had UCB recurrence and 82 patients (41.4%) died from the disease. In multivariable analyses that adjusted for the effects of pathological tumour stage, grade, LVI, lymph node metastasis and adjuvant chemotherapy, HER-2 positive patients were at increased risk for both UCB recurrence (hazard ratio [HR] 1.955, P= 0.003) and UCB-specific mortality (HR 2.066, P= 0.004) compared with patients with negative HER-2 expression.
  
  
  CONCLUSIONS
  a positive HER-2 status is associated with aggressive UCB and provides independent prognostic information for UCB recurrence and mortality. Assessment of HER-2 status can be used to identify patients at high risk of disease progression who may benefit from adjuvant HER-2-targeted mono- or combined therapy after RC.
authors.affiliation: Departments of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Bolenz
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.forename: Raheela
authors.initials: R
authors.lastname: Ashfaq
authors.forename: Richard
authors.initials: R
authors.lastname: Ho
authors.forename: Arthur I
authors.initials: AI
authors.lastname: Sagalowsky
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D015653:Cystectomy / Q000379:methods*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012307:Risk Factors; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases