Expression of Mcl-1 splicing variants in clear-cell renal cancer and their correlation with histopathological parameters and prognosis.
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.
Kempkensteffen
Carsten
C
Department of Urology, Charité - Universitätsmedizin Berlin, Berlin, Germany. carsten.kempkensteffen@charite.de
Hinz
Stefan
S
Johannsen
Manfred
M
Krause
Hans
H
Magheli
Ahmed
A
Christoph
Frank
F
Köllermann
Jens
J
Schrader
Mark
M
Schostak
Martin
M
Miller
Kurt
K
Weikert
Steffen
S
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
D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2