title: Expression of Mcl-1 splicing variants in clear-cell renal cancer and their correlation with histopathological parameters and prognosis.
abstract: OBJECTIVE
  Altered expression of the Bcl-2 family member Mcl-1 has been linked to the progression and outcome of various malignancies, but its expression and potential prognostic value has yet not been investigated in clear-cell renal cell carcinomas (ccRCC).
  
  
  METHODS
  In this study, dual-colour real-time RT-PCR was used to quantify the expression of Mcl-1 splicing variants in malignant and paired normal renal tissue samples, obtained from 93 ccRCC patients (median follow-up: 45 months) undergoing radical nephrectomy.
  
  
  RESULTS
  Over-expression of the anti-apoptotic Mcl-1L variant in ccRCC occurred in nearly 60% of the paired samples (p = 0.004). Decreased expression, however, was related to poor tumour differentiation (p = 0.013) and independently predicted a higher risk for relapse (hazard rate 3.99; 95% CI 1.32-12.04; p = 0.014). Kaplan-Meier analyses revealed down-regulation of Mcl-1L in ccRCC to be associated with a markedly shortened recurrence-free and disease-specific survival, particularly in patients with locally advanced (p < 0.001 and p = 0.003) and poorly differentiated tumours (p = 0.004 and p = 0.011).
  
  
  CONCLUSIONS
  These findings suggest Mcl-1L to provide a molecular parameter for outcome prediction in ccRCC patients, down-regulation indicating exceptionally aggressive tumour phenotypes.
authors.affiliation: Department of Urology, Charité - Universitätsmedizin Berlin, Berlin, Germany. carsten.kempkensteffen@charite.de
authors.forename: Carsten
authors.initials: C
authors.lastname: Kempkensteffen
authors.forename: Stefan
authors.initials: S
authors.lastname: Hinz
authors.forename: Manfred
authors.initials: M
authors.lastname: Johannsen
authors.forename: Hans
authors.initials: H
authors.lastname: Krause
authors.forename: Ahmed
authors.initials: A
authors.lastname: Magheli
authors.forename: Frank
authors.initials: F
authors.lastname: Christoph
authors.forename: Jens
authors.initials: J
authors.lastname: Köllermann
authors.forename: Mark
authors.initials: M
authors.lastname: Schrader
authors.forename: Martin
authors.initials: M
authors.lastname: Schostak
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.forename: Steffen
authors.initials: S
authors.lastname: Weikert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D012326:RNA Splicing
chemical_list: D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2