title: Her2 amplification distinguishes a subset of non-muscle-invasive bladder cancers with a high risk of progression.
abstract: BACKGROUND
  Several studies have employed immunohistochemistry to detect Her2/neu overexpression in urothelial carcinomas, yielding a tremendous range of positive expression rates. Few studies have examined Her2 status in non-muscle invasive bladder cancer (NMIBC) using fluorescence in situ hybridisation (FISH).
  
  
  OBJECTIVE
  To evaluate Her2 amplification in NMIBC (Ta/T1), to correlate the findings with recurrence and progression, and compare the Her2 status between primary and progressive tumours.
  
  
  METHODS
  FISH and immunohistochemistry for Her2/neu were performed on tissue arrays consisting of 36 papillary urothelial neoplasms of low malignant potential (PUNLMPs), 190 low grade urothelial carcinomas (LG-UCs) and 178 high grade urothelial carcinomas (HG-UCs). 32 cases with specimens of both primary and progressive tumours (from Ta/T1 to T2-4) were included for comparative analyses.
  
  
  RESULTS
  16 HG-UCs (9.0%) showed Her2 gene amplification while none of the PUNLMPs and LG-UCs showed this aberration. There was 100% concordance in the status of Her2 amplification between primary and progressive lesions. Immunohistochemistry and FISH results were in closest agreement when overexpression was defined as 50% of tumour cells showing immunoreactivity. The cumulative incidences of recurrence and progression in Her2-amplified HG-UC were significantly higher than in those without amplification.
  
  
  CONCLUSIONS
  A subset of high-grade NMIBCs contain Her2 amplification and are associated with markedly aggressive behaviour. Her2 diagnostics are valuable for distinguishing patients who require diligent surveillance and would potentially benefit from anti-Her2 therapies.
authors.affiliation: Department of Pathology, Taipei Veterans General Hospital & National Yang-Ming University, Taipei, Taiwan. ccpan@vghtpe.gov.tw
authors.forename: Paul Chih-Hsueh
authors.initials: PC
authors.lastname: Chen
authors.forename: Hui-Jung
authors.initials: HJ
authors.lastname: Yu
authors.forename: Yen-Hwa
authors.initials: YH
authors.lastname: Chang
authors.forename: Chin-Chen
authors.initials: CC
authors.lastname: Pan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D002277:Carcinoma / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D016009:Chi-Square Distribution; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human