title: Identification of high-risk patients with clear cell renal cell carcinoma based on interphase-FISH.
abstract: BACKGROUND
  The aim of this study was to examine the prognostic value of four significant aberrations based on our previous studies by array-CGH to develop a prognostic Fluorescence-in situ-hybridisation (FISH) assay for clear cell renal cell carcinomas (ccRCC).
  
  
  METHODS
  Fluorescence-in situ-hybridisation experiments were performed on 100 ccRCCs (52 metastasised out of 48 non-metastasised). The mean/median follow up of patients was 59/54 months. Commercially available FISH probes were used for each critical chromosomal region (1q21.3, 7q36.3, 9p21.3p24.1 and 20q11.21q13.32). The total number of specific aberrations (TNSA) was calculated for each tumour based on the specific genomic alterations.
  
  
  RESULTS
  Total number of specific aberrations was the best predictor of metastasis (area under the curve (AUC)=0.814) compared with single aberrations (AUC: 0.619-0.708) and to 11 different combinations of these 4 aberrations in the receiver operating characteristic curve analysis. Total number of specific aberrations, tumour grade and tumour size were independent predictors of metastasis in the multivariate analysis (P<0.001) for the whole cohort as well as for organ-confined tumours. Total number of specific aberrations and grade could also independently predict cancer-specific mortality (CSM). Total number of specific aberrations demonstrated the highest significance in COX proportional hazard models of overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS).
  
  
  CONCLUSIONS
  We identified TNSA as an independent prognostic factor which is associated with metastasis occurrence, CSM, OS, CSS and PFS in patients with ccRCCs.
authors.affiliation: Department of Urology, Jena University Hospital, Jena, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Sanjmyatav
authors.affiliation: Department of Urology, Jena University Hospital, Jena, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Matthes
authors.affiliation: Department of Urology, Jena University Hospital, Jena, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Muehr
authors.affiliation: Department of Urology, Jena University Hospital, Jena, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Sava
authors.affiliation: Department of Urology, Jena University Hospital, Jena, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Sternal
authors.affiliation: Department of Urology, Jena University Hospital, Jena, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Wunderlich
authors.affiliation: Institute of Pathology, Jena University Hospital, Jena, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Gajda
authors.affiliation: Department of Urology, Jena University Hospital, Jena, Germany.
authors.forename: M-O
authors.initials: MO
authors.lastname: Grimm
authors.affiliation: 1] Department of Urology, Jena University Hospital, Jena, Germany [2] Clinic of Urology and Pediatric Urology, Saarland University Medical Center, Homburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Junker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002869:Chromosome Aberrations; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D012189:Retrospective Studies; D018570:Risk Assessment