Institute of Pathology, University of Basel, Basel, Switzerland.
Leuk Lymphoma. 2010 Feb;51(2):199-212. doi: 10.3109/10428190903370338.
A number of biomarkers, particularly proteins that contribute to prognosis in diffuse large B cell lymphoma (DLBCL), have been identified. However, translation into accepted standards to predict survival has not yet been accomplished, primarily due to contradictory reports in the literature resulting from, among other factors, arbitrary methodologies used to set cut-off values for determining positivity. Some of these problems might be resolved by application of rational statistical methods for determination of cut-off scores. Herein, we critically address issues on in situ phenotypic prognostic tumor-related biomarkers in DLBCL with a particular and practical emphasis on tools for cut-off level determination, especially receiver operating characteristic curve analysis. Moreover, we candidly illustrate the application of these tools for efficient disease-specific survival prognostication on a tissue microarray collective of 240 primary DLBCL using the common prognostic biomarkers Bcl-2, Bcl-6, CD10, FOXP1, MUM1, and Cyclin E. Comparison of the results relative to disease-specific survival unequivocally showed the superior discriminatory power of the cut-off levels calculated by receiver operating curves and the Youden's index, compared to arbitrary cut-off values from the literature, advocating fundamental application of rational methods for determination of clinically relevant prognostic biomarkers' cut-off scores.
已经确定了许多生物标志物，特别是在弥漫性大 B 细胞淋巴瘤（DLBCL）中有助于预后的蛋白质。然而，尚未将其转化为可接受的标准来预测生存，主要是由于文献中的相互矛盾的报告，这些报告主要是由于用于确定阳性的截止值的任意方法学因素造成的。通过应用合理的统计方法来确定截止分数，可以解决其中的一些问题。在这里，我们批判性地讨论了 DLBCL 中肿瘤相关生物标志物的原位表型预后问题，特别强调了用于确定截止水平的工具，特别是接收者操作特征曲线分析。此外，我们诚实地说明了这些工具在使用常见预后生物标志物 Bcl-2、Bcl-6、CD10、FOXP1、MUM1 和 Cyclin E 对 240 例原发性 DLBCL 的组织微阵列进行的高效疾病特异性生存预后中的应用。与疾病特异性生存的结果进行比较，明确显示了通过接收者操作曲线和 Youden 指数计算的截止水平的卓越判别能力，与文献中的任意截止值相比，支持为确定临床相关预后生物标志物的截止分数而应用合理方法的基本原理。
