title: Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery.
abstract: BACKGROUND
  Wider clinical applications of 9p status in clear cell renal cell carcinoma (ccRCC) are limited owing to the lack of validation and consensus for interphase fluorescent in situ hybridisation (I-FISH) scoring technique. The aim of this study was to analytically validate the applicability of I-FISH in assessing 9p deletion in ccRCC and to clinically assess its long-term prognostic impact following surgical excision of ccRCC.
  
  
  METHODS
  Tissue microarrays were constructed from 108 renal cell carcinoma (RCC) tumour paraffin blocks. Interphase fluorescent in situ hybridisation analysis was undertaken based on preset criteria by two independent observers to assess interobserver variability. 9p status in ccRCC tumours was determined and correlated to clinicopathological variables, recurrence-free survival and disease-specific survival.
  
  
  RESULTS
  There were 80 ccRCCs with valid 9p scoring and a median follow-up of 95 months. Kappa statistic for interobserver variability was 0.71 (good agreement). 9p deletion was detected in 44% of ccRCCs. 9p loss was associated with higher stage, larger tumours, necrosis, microvascular and renal vein invasion, and higher SSIGN (stage, size, grade and necrosis) score. Patients with 9p-deleted ccRCC were at a higher risk of recurrence (P=0.008) and RCC-specific mortality (P=0.001). On multivariate analysis, 9p deletion was an independent predictor of recurrence (hazard ratio 4.323; P=0.021) and RCC-specific mortality (hazard ratio 4.603; P=0.007). The predictive accuracy of SSIGN score improved from 87.7% to 93.1% by integrating 9p status to the model (P=0.001).
  
  
  CONCLUSIONS
  Loss of 9p is associated with aggressive ccRCC and worse prognosis in patients following surgery. Our findings independently confirm the findings of previous reports relying on I-FISH to detect 9p (CDKN2A) deletion.
authors.affiliation: Academic section of Urology, Medical Research Institute, School of Medicine, University of Dundee, Dundee DD1 9SY, UK.
authors.forename: I
authors.initials: I
authors.lastname: El-Mokadem
authors.affiliation: Academic section of Urology, Medical Research Institute, School of Medicine, University of Dundee, Dundee DD1 9SY, UK.
authors.forename: J
authors.initials: J
authors.lastname: Fitzpatrick
authors.affiliation: Academic section of Urology, Medical Research Institute, School of Medicine, University of Dundee, Dundee DD1 9SY, UK.
authors.forename: J
authors.initials: J
authors.lastname: Bondad
authors.affiliation: Division of Population Sciences, Medical Research Institute, School of Medicine, University of Dundee, Dundee DD1 9SY, UK.
authors.forename: P
authors.initials: P
authors.lastname: Rauchhaus
authors.affiliation: Department of Clinical Genetics, NHS Tayside Health Board, Dundee DD1 9SY, UK.
authors.forename: J
authors.initials: J
authors.lastname: Cunningham
authors.affiliation: Department of Clinical Genetics, NHS Tayside Health Board, Dundee DD1 9SY, UK.
authors.forename: N
authors.initials: N
authors.lastname: Pratt
authors.affiliation: Department of Pathology, Medical Research Institute, School of Medicine, Dundee DD1 9SY, UK.
authors.forename: S
authors.initials: S
authors.lastname: Fleming
authors.affiliation: Academic section of Urology, Medical Research Institute, School of Medicine, University of Dundee, Dundee DD1 9SY, UK.
authors.forename: G
authors.initials: G
authors.lastname: Nabi
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000517:prevention & control; D016016:Proportional Hazards Models