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弥漫性大B细胞非霍奇金淋巴瘤中凋亡调控和增殖控制基因的遗传损伤特征分析。

Characterization of genetic lesions in apoptosis-regulating and proliferation control genes in diffuse large B-cell non-Hodgkin's lymphoma.

作者信息

Pervez Shahid, Nasir Muhammd I, Moatter Tariq, Ahsan Adeeb, Haq Amna, Siddiqui Tariq

机构信息

Department of Pathology and Microbiology, Aga Khan University Medical Centre, Karachi, Pakistan.

出版信息

J Cancer Res Ther. 2009 Oct-Dec;5(4):254-62. doi: 10.4103/0973-1482.59901.

DOI:10.4103/0973-1482.59901
PMID:20160358
Abstract

BACKGROUND

This study was conducted to analyze the frequency, expression patterns, and the impact of individual proteins BCL2, BCL6, and p53 on overall survival (OS) in adult, diffuse large B-cell lymphoma (DLBCL) patients. BCL2 gene was further investigated for potential alterations at the DNA level and correlated with OS.

MATERIALS AND METHODS

A total of 117 adult well-characterized DLBCL cases were included. The panel of antibodies comprised CD45, CD20, CD79a, CD3, BCL2, BCL6, and p53. PCR was also employed to correlate the events at the DNA level in BCL2.

RESULTS

The mean and median ages were 47.74 and 49 with a M:F ratio of 2.07:1. The incidence of BCL2, BCL6, and p53 expression was observed in 64.10%, 37.60%, and 52.13% of cases, respectively. Amplifiable quality DNA was available from 90 cases. BCL2/IGH translocation was found in 35/90 patients (38.88%) with 24 cases showing BCL2 (MBR)/IGH and 11 cases BCL2 (mcr)/IGH translocation. No association between BCL2 overexpression and BCL2 /IGH translocation was seen. Clinical data were available for 52 patients treated by CHOP therapy. It was found that patients with p53 overexpression had decreased overall survival (P = 0.0004) whereas BCL2, BCL6 expression, and BCL2/IGH translocation had no impact on overall survival.

CONCLUSION

Our data suggest that simple p53 protein expression by IHC at the time of diagnosis may help to identify high-risk patients, who may benefit with more aggressive and newer treatments in addition to standard CHOP.

摘要

背景

本研究旨在分析成年弥漫性大B细胞淋巴瘤(DLBCL)患者中个体蛋白BCL2、BCL6和p53的表达频率、模式及其对总生存期(OS)的影响。进一步研究BCL2基因在DNA水平的潜在改变及其与总生存期的相关性。

材料与方法

共纳入117例特征明确的成年DLBCL病例。抗体组合包括CD45、CD20、CD79a、CD3、BCL2、BCL6和p53。还采用聚合酶链反应(PCR)来关联BCL2基因在DNA水平的事件。

结果

平均年龄和中位数年龄分别为47.74岁和49岁,男女比例为2.07:1。BCL2、BCL6和p53表达的发生率分别在64.10%、37.60%和52.13%的病例中观察到。90例病例可获得可扩增的高质量DNA。在90例患者中有35例(38.88%)发现BCL2/IGH易位,其中24例显示BCL2(主要断裂区域,MBR)/IGH易位,11例显示BCL2(次要断裂区域,mcr)/IGH易位。未发现BCL2过表达与BCL2/IGH易位之间存在关联。有52例接受CHOP方案治疗的患者的临床数据可用。发现p53过表达的患者总生存期降低(P = 0.0004),而BCL2、BCL6表达及BCL2/IGH易位对总生存期无影响。

结论

我们的数据表明,诊断时通过免疫组化检测p53蛋白的简单表达可能有助于识别高危患者,这些患者除标准CHOP方案外,可能从更积极的新型治疗中获益。

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