Bcl-2是乳腺癌的一个预后标志物，独立于诺丁汉预后指数。

Bcl-2 is a prognostic marker in breast cancer independently of the Nottingham Prognostic Index.

作者信息

Callagy Grace M, Pharoah Paul D, Pinder Sarah E, Hsu Forrest D, Nielsen Torsten O, Ragaz Joseph, Ellis Ian O, Huntsman David, Caldas Carlos

机构信息

Cancer Genomics Program, Department of Oncology, Hutchison-Medical Research Council Research Centre, University of Cambridge, United Kingdom.

出版信息

Clin Cancer Res. 2006 Apr 15;12(8):2468-75. doi: 10.1158/1078-0432.CCR-05-2719.

DOI:10.1158/1078-0432.CCR-05-2719

PMID:16638854

Abstract

PURPOSE

Prognostication of breast cancer using clinicopathologic variables, although useful, remains imperfect. Many reports suggest that gene expression profiling can refine the current approach. Alternatively, it has been shown that panels of proteins assessed by immunohistochemistry might also be useful in this regard. We evaluate the prognostic potential of a panel of markers by immunohistochemistry in a large case series to establish if either a single marker or a panel could improve the prognostic power of the Nottingham Prognostic Index (NPI). We validated the results in an independent series.

EXPERIMENTAL DESIGN AND RESULTS

The expression of 13 biomarkers was evaluated in 930 breast cancers on a tissue microarray. Eight markers [estrogen receptor (ER), progesterone receptor (PR), Bcl-2, cyclin E, p53, MIB-1, cytokeratin 5/6, and HER2] showed a significant association with survival at 10 years on univariate analysis. On multivariate analysis that included these eight markers and the NPI, only the NPI [hazard ratio (HR), 1.35; 95% confidence interval (95% CI), 1.16-1.56; P = 0.0005], ER (HR, 0.59; 95% CI, 0.39-0.88; P = 0.011), and Bcl-2 (HR, 0.68; 95% CI, 0.46-0.99; P = 0.055) were significant. In a subsequent multivariate analysis that included the NPI, ER, and Bcl-2, only Bcl-2 (HR, 0.62; 95% CI, 0.44-0.87; P = 0.006) remained independent of NPI (HR, 1.50; 95% CI, 1.16-1.56; P = 0.004). In addition, Bcl-2, used as a single marker, was more powerful than the use of a panel of markers. Based on these results, an independent series was used to validate the prognostic significance of Bcl-2. ER and PR were also evaluated in this validation series. Bcl-2 (HR, 0.83; 95% CI, 0.71-0.96; P = 0.018) retained prognostic significance independent of the NPI (HR, 2.04; 95% CI, 1.67-2.51; P < 0.001) with an effect that was maximal in the first 5 years.

CONCLUSION

Bcl-2 is an independent predictor of breast cancer outcome and seems to be useful as a prognostic adjunct to the NPI, particularly in the first 5 years after diagnosis.

摘要

目的

利用临床病理变量对乳腺癌进行预后评估虽有帮助，但仍不完善。许多报告表明，基因表达谱分析可优化当前方法。另外，已有研究显示，通过免疫组织化学评估的蛋白质组也可能在这方面有用。我们在一个大型病例系列中通过免疫组织化学评估一组标志物的预后潜力，以确定单一标志物或一组标志物是否能提高诺丁汉预后指数（NPI）的预后评估能力。我们在一个独立系列中验证了结果。

实验设计与结果

在组织芯片上对930例乳腺癌评估了13种生物标志物的表达。单因素分析显示，8种标志物[雌激素受体（ER）、孕激素受体（PR）、Bcl-2、细胞周期蛋白E、p53、MIB-1、细胞角蛋白5/6和HER2]与10年生存率显著相关。在包含这8种标志物和NPI的多因素分析中，只有NPI[风险比（HR），1.35；95%置信区间（95%CI），1.16 - 1.56；P = 0.0005]、ER（HR，0.59；95%CI，0.39 - 0.88；P = 0.011）和Bcl-2（HR，0.68；95%CI，0.46 - 0.99；P = 0.055）具有显著性。在随后包含NPI、ER和Bcl-2的多因素分析中，只有Bcl-2（HR，0.62；95%CI，0.44 - 0.87；P = 0.006）独立于NPI（HR，1.50；95%CI，1.16 - 1.56；P = 0.004）。此外，Bcl-2作为单一标志物比一组标志物更具评估能力。基于这些结果，使用一个独立系列来验证Bcl-2的预后意义。在这个验证系列中也评估了ER和PR。Bcl-2（HR，0.83；95%CI，0.71 - 0.96；P = 0.018）独立于NPI（HR，2.04；95%CI，1.67 - 2.51；P < 0.001）保留了预后意义，其影响在诊断后的前5年最大。