Renal cell carcinoma MIB-1, bax and Bcl-2 expression and prognosis

Renal cell carcinoma MIB-1, bax and Bcl-2 expression and prognosis
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DOI:
10.1097/01.ju.0000144334.97639.bf
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发表时间:
2004-12-01
期刊:
影响因子:
6.6
通讯作者:
Martikainen, PM
Martikainen, PM
中科院分区:
医学1区
文献类型:
--
作者:
Kallio, JP;Hirvikoski, P;Martikainen, PM

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目的:增殖和程序性细胞死亡(凋亡)是肿瘤发生和发展的关键因素。在癌发生中,重要的细胞凋亡调节因子是Bcl-2家族的成员。在这个家族中,Bcl-2基因对细胞凋亡具有抑制作用,而Bax促进细胞死亡。在肾细胞癌(RCC)中,Bcl-2蛋白与RCC预后的关系一直存在争议。我们评估Bax和Bcl-2在RCC的水平,其与预后,增殖和传统的预后factors.Materials和方法:我们的前瞻性研究人群包括138例连续进行根治性肾切除术的RCC患者。Ki-67(MIB-1),Bax和Bcl-2的免疫染色和半定量指标进行了估计。探讨了它们与预后的关系。在单变量分析中,根据生存率,Bax实现了统计学显著差异(阳性vs阴性HR 3.04,95% CI 1.27 - 7.23),Bcl-2(阳性vs阴性HR 0.43,95%v CI 0.23 - 0.81),MIB-1(连续HR 1.03,95% CI 1.001 - 1.064),Fuhrman核分级(4 vs 1 + 2 HR 8.15,95% CI 3.13 - 21.20)和分期(4 vs 1 HR 60.04,95% CI 13.99 - 257.68)。必经阶段(HR 47.96,95% CI 10.85 - 212.03)和Fuhrman分级(HR 4.32,95%CI 1.60 ~ 11.65)在考克斯回归多因素分析中达到统计学显著性。结论:在我们的前瞻性研究中,Bax和Bcl-2与肾细胞癌的预后有统计学显著性相关,但没有达到独立预后因素的地位。需要进一步的研究来阐明凋亡过程在肿瘤进展和预后中的作用。
Purpose: Proliferation and programmed cell death (apoptosis) are key factors in oncogenesis and tumor progression. In carcinogenesis important regulators of apoptosis are members of the Bcl-2 family. In this family the Bcl-2 gene has an inhibitory effect on apoptosis, while Bax promotes cell death. In renal cell carcinoma (RCC) the associations between Bcl-2 proteins and RCC prognosis have been controversial. We evaluated Bax and Bcl-2 levels in RCC, and their associations with prognosis, proliferation and traditional prognostic factors.Materials and Methods: Our prospective study population comprised 138 consecutive patients who underwent radical nephrectomy for RCC. Immunostaining and semiquantitative indices for Ki-67 (MIB-1), Bax and Bcl-2 were estimated. Their associations with prognosis were explored.Results: On univariate analysis according to survival statistically significant differences were achieved by Bax (positive vs negative HR 3.04, 95% CI 1.27 to 7.23), Bcl-2 (positive vs negative HR 0.43, 95%v CI 0.23 to 0.81), MIB-1 (continuous HR 1.03, 95% CI 1.001 to 1.064), Fuhrman nuclear class (4 vs 1 plus 2 HR 8.15, 95% CI 3.13 to 21.20) and stage (4 vs 1 HR 60.04, 95% CI 13.99 to 257.68). Only stage (HR 47.96, 95% CI 10.85 to 212.03) and Fuhrman classification (HR 4.32, 95% CI 1.60 to 11.65) attained statistical significance on Cox regression multivariate analysis.Conclusions: In our prospective study Bax and Bcl-2 showed a statistically significant association with prognosis in RCC but did not achieve the status of independent prognostic factors. Further studies are needed to clarify the role of the apoptotic process in tumor progression and prognosis.