title: Assessment of human epidermal growth factor receptor 2 status in urothelial carcinoma of the upper urinary tract: a study using dual-color in situ hybridization and immunohistochemistry.
abstract: OBJECTIVE
  Upper urinary tract urothelial carcinoma (UUTUC) is an uncommon neoplasm frequently discovered at a high-stage disease. The prognosis of disseminated UUTUCs is poor despite the use of platinum-based chemotherapy. The aim of the study was to evaluate HER2 overexpression and amplification in a series of 83 UUTUCs.
  
  
  METHODS
  All tumors were formalin fixed. TNM stage, grade, lymphovascular invasion, surgical margins, morphologic variants were reviewed by 2 pathologists. All tumors were immunostained with anti-HER2 antibody. HER2 gene amplification was determined by dual-color in situ hybridization. Gene amplification was defined by an HER2/CEN 17 ratio >2.2.
  
  
  RESULTS
  HER2 immunostaining was observed in 33/83 tumors. Twelve cases were 2+ score and 2 cases were 3+ score. HER2 in situ hybridization was evaluable in 75/83 cases. Amplification was observed in 6 (7%) cases. All amplified tumors were of high grade and 4/6 were stage pT3. A strong correlation between HER2 overexpression and amplification was noted (P<0.0001). HER2 overexpression and amplification were correlated with the pN+ stage but not with specific survival or recurrence.
  
  
  CONCLUSIONS
  These results suggest that HER2 amplification is a rare event in UUTUC but may be of interest for targeted therapy in selected high-grade and high-stage tumors.
authors.affiliation: Institute of Pathology, Biology-Pathology Center, Centre Hospitalier Regional Universitaire and University Lille II, Lille, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Vershasselt-Crinquette
authors.forename: Pierre
authors.initials: P
authors.lastname: Colin
authors.forename: Adil
authors.initials: A
authors.lastname: Ouzzane
authors.forename: Viviane
authors.initials: V
authors.lastname: Gnemmi
authors.forename: Yves-Marie
authors.initials: YM
authors.lastname: Robin
authors.forename: Sebastien
authors.initials: S
authors.lastname: Aubert
authors.forename: Arnauld
authors.initials: A
authors.lastname: Villers
authors.forename: Xavier
authors.initials: X
authors.lastname: Leroy
mesh_terms: D000368:Aged; D002277:Carcinoma / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012008:Recurrence; D016019:Survival Analysis; D015854:Up-Regulation; D014571:Urologic Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D019459:Urothelium / Q000378:metabolism* / Q000473:pathology
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human