Expression of Mcl-1 splicing variants in clear-cell renal cancer and their correlation with histopathological parameters and prognosis.
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Expression of Mcl-1 splicing variants in clear-cell renal cancer and their correlation with histopathological parameters and prognosis. / Kempkensteffen, Carsten; Hinz, Stefan; Johannsen, Manfred; Krause, Hans; Magheli, Ahmed; Christoph, Frank; Köllermann, Jens; Schrader, Mark; Schostak, Martin; Miller, Kurt; Weikert, Steffen.
In: TUMOR BIOL, Vol. 30, No. 2, 2, 2009, p. 73-79.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Expression of Mcl-1 splicing variants in clear-cell renal cancer and their correlation with histopathological parameters and prognosis.
AU - Kempkensteffen, Carsten
AU - Hinz, Stefan
AU - Johannsen, Manfred
AU - Krause, Hans
AU - Magheli, Ahmed
AU - Christoph, Frank
AU - Köllermann, Jens
AU - Schrader, Mark
AU - Schostak, Martin
AU - Miller, Kurt
AU - Weikert, Steffen
PY - 2009
Y1 - 2009
N2 - BACKGROUND/AIMS: 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). CONCLUSION: These findings suggest Mcl-1L to provide a molecular parameter for outcome prediction in ccRCC patients, down-regulation indicating exceptionally aggressive tumour phenotypes.
AB - BACKGROUND/AIMS: 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). CONCLUSION: These findings suggest Mcl-1L to provide a molecular parameter for outcome prediction in ccRCC patients, down-regulation indicating exceptionally aggressive tumour phenotypes.
M3 - SCORING: Zeitschriftenaufsatz
VL - 30
SP - 73
EP - 79
JO - TUMOR BIOL
JF - TUMOR BIOL
SN - 1010-4283
IS - 2
M1 - 2
ER -
