BCL-2 family proteins in peripheral T-cell lymphomas: correlation with tumour apoptosis and proliferation
BCL-2 family proteins in peripheral T-cell lymphomas: correlation with tumour apoptosis and proliferation
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DOI：
10.1002/path.1346
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发表时间：
2003-06-01
影响因子：
7.3
通讯作者：
Medeiros, LJ
中科院分区：
文献类型：
--
作者：
Rassidakis, GZ;Jones, D;Medeiros, LJ
本研究调查了抗凋亡蛋白BCL-2，BCL-XL和MCL-1和促凋亡蛋白BAX和BCL-XS的表达水平在一系列的112例外周T细胞淋巴瘤（PTCL）根据WHO分类。使用免疫组织化学方法和10%的截止值，在PTCL的子集中检测到每种蛋白质：BCL-2为46%，BCL-XS为49%，BAX为57%，BCL-XL为57%，MCL-1为65%。这些蛋白的阳性细胞的平均百分比在PTCL类型之间变化显著。只有两种类型的PTCL，ALK阳性间变性大细胞淋巴瘤（ALCL）和肠病型T细胞淋巴瘤，有一个独特的表达模式;所有的BCL-2阴性和MCL-1阳性。ALK阳性ALCL中BAX阳性和BCL-XS阳性肿瘤细胞的平均百分比高于ALK阴性ALCL或其他类型的PTCL（分别为p = 0.06和p = 0.01，Kruskal-Wallis检验）。在ALK阳性ALCL和ALK阴性ALCL中，MCL-1的检出频率（p = 0.01，卡方检验）和水平（p = 0.0001，Kruskal-Wallis检验）显著高于其他PTCL类型。凋亡率，通过TUNEL法评估，与BCL-2表达呈负相关（p = 0.035）。通过MIB-1抗体评估的增殖指数与MCL-1（R = 0.42，p = 0.003）、BCL-2（R = 0.32，p = 0.027）、BAX（R = 0.33，p = 0.014）和BCL-XL（R = 0.34，p = 0.015）的表达水平相关（斯皮尔曼等级）。总之，BCL-2家族蛋白表达的PTCL的一个子集和他们的水平与一些组织学类型，凋亡率和增殖指数。这些蛋白质的表达可以解释许多类型的PTCL对标准化疗的不良反应。这些蛋白质也可能为实验性治疗提供新的靶点。版权所有（C）2003约翰威利父子有限公司。
The present study investigated expression levels of the anti-apoptotic proteins BCL-2, BCL-XL and MCL-1 and the pro-apoptotic proteins BAX and BCL-XS in a series of 112 peripheral T-cell lymphomas (PTCLs) classified according to the WHO classification. Using immunohistochemical methods and a 10% cut-off, each protein was detected in a subset of PTCLs: BCL-2 in 46%, BCL-XS in 49%, BAX in 57%, BCL-XL in 57%, and MCL-1 in 65%. The mean percentage of positive cells for these proteins varied significantly among the PTCL types. Only two types of PTCL, ALK-positive anaplastic large cell lymphoma (ALCL) and enteropathy-type T-cell lymphoma, had a distinctive pattern of expression; all were BCL-2-negative and MCL-1-positive. The mean percentage of BAX-positive and BCL-XS-positive tumour cells was higher in ALK-positive ALCL than in ALK-negative ALCL or other types of PTCL (p = 0.06 and p = 0.01, respectively, Kruskal-Wallis test). MCL-1 was detected significantly more frequently (p = 0.01, chi-square test) and at higher levels (p = 0.0001, Kruskal-Wallis test) in ALK-positive ALCL and ALK-negative ALCL than in other PTCL types. The apoptotic rate, evaluated by the TUNEL assay, correlated inversely with BCL-2 expression (p = 0.035). The proliferation index, assessed by the MIB-1 antibody, correlated with expression levels of MCL-1 (R = 0.42, p = 0.003), BCL-2 (R = 0.32, p = 0.027), BAX (R = 0.33, p = 0.014), and BCL-XL (R = 0.34, p = 0.015) (Spearman rank). In conclusion, BCL-2 family proteins are expressed by a subset of PTCLs and their levels correlate with some histological types, apoptotic rate, and proliferation index. Expression of these proteins may explain the poor response of many types of PTCL to standard chemotherapy. These proteins may also provide novel targets for experimental therapy. Copyright (C) 2003 John Wiley Sons, Ltd.