title: Prognostic implications of sarcomatoid and rhabdoid differentiation in patients with grade 4 renal cell carcinoma.
abstract: OBJECTIVE
  Sarcomatoid and rhabdoid differentiation are associated with poor outcomes in renal cell carcinoma (RCC). We examined the impact of differentiation on cancer-specific survival (CSS) in surgically treated patients with grade 4 RCC.
  
  
  METHODS
  Using our institutional database of 1176 nephrectomies from 2005 to 2013, we identified patients with grade 4 RCC or any grade and the presence of sarcomatoid or rhabdoid differentiation. We divided the cohort based on differentiation: no differentiation, rhabdoid only, sarcomatoid only, and sarcomatoid and rhabdoid. CSS was analyzed using the Kaplan-Meier method and Cox proportional hazards modeling.
  
  
  RESULTS
  Of 264 patients with grade 4 RCC, 159 (60.2 %) exhibited differentiation, including 45 (28.3 %) with rhabdoid only, 87 (54.7 %) with sarcomatoid only, and 27 (16.9 %) with rhabdoid and sarcomatoid. Sarcomatoid differentiation, either alone or with rhabdoid differentiation, was associated with worse median CSS than no differentiation (1.1 vs. 3.3 years, p < 0.01, and 0.9 vs. 3.3 years, p < 0.01, respectively). In patients with non-metastatic (HR 1.95, 95 % CI 1.19-3.19, p = 0.008) and metastatic (HR 2.22, 95 % CI 1.45-3.41, p < 0.001) RCC, sarcomatoid differentiation was associated with an increased risk of cancer-specific death. On multivariable analysis, sarcomatoid differentiation was an independent predictor of RCC death in patients with non-metastatic (HR 1.72, 95 % CI 1.04-2.84, p = 0.03) and metastatic (HR 1.74, 95 % CI 1.05-2.90, p = 0.03) disease. Rhabdoid differentiation alone was not associated with worse CSS (p = 0.55).
  
  
  CONCLUSIONS
  In grade 4 RCC, sarcomatoid differentiation is associated with increased mortality risk across all stages of disease. Rhabdoid differentiation is not associated with additional mortality risk.
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44016, USA.
authors.forename: Onder
authors.initials: O
authors.lastname: Kara
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44016, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Maurice
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44016, USA.
authors.forename: Homayoun
authors.initials: H
authors.lastname: Zargar
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44016, USA.
authors.forename: Ercan
authors.initials: E
authors.lastname: Malkoc
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44016, USA.
authors.forename: Oktay
authors.initials: O
authors.lastname: Akca
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44016, USA.
authors.forename: Hiury S
authors.initials: HS
authors.lastname: Andrade
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44016, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ramirez
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44016, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Caputo
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44016, USA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Nelson
authors.affiliation: Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Rini
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44016, USA. Kaoukj@ccf.org.
authors.forename: Jihad H
authors.initials: JH
authors.lastname: Kaouk
mesh_terms: D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D002292:Carcinoma, Renal Cell / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D002423:Cause of Death; D002454:Cell Differentiation; D016208:Databases, Factual; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009392:Nephrectomy / Q000379:methods* / Q000401:mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018335:Rhabdoid Tumor / Q000473:pathology; D018570:Risk Assessment; D012509:Sarcoma / Q000473:pathology; D018709:Statistics, Nonparametric; D015996:Survival Rate
keywords: Prognostic; Renal cell carcinoma (RCC); Rhabdoid differentiation; Sarcomatoid differentiation