原发性淋巴结弥漫性大B细胞淋巴瘤：生物学预后因素的鉴定

De novo nodal diffuse large B-cell lymphoma: identification of biologic prognostic factors.

作者信息

Abd El-Hameed Amany

机构信息

The Department of Pathology, NCI, Cairo University, Cairo.

出版信息

J Egypt Natl Canc Inst. 2005 Mar;17(1):20-8.

PMID:16353079

Abstract

BACKGROUND

Diffuse large B-cell Lymphoma (DLBCL) represents the most frequent type of non-Hodgkin lymphoma (NHL). Although combination chemotherapy has improved the outcome, long-term cure is now possible for approximately 50% of all patients, making the search for parameters identifying patients at high risk particularly needed. The presence of bcl-2 gene rearrangement in de novo DLBCL suggests a possible follicle center cell origin and perhaps a distinct clinical behavior. This study investigated the frequency and prognostic significance of t(14;18) translocation and bcl-2 protein overexpression in a cohort of patients with de novo nodal DLBCL who where uniformly evaluated and treated.

MATERIAL AND METHODS

A total of 40 patients with de novo nodal DLBCL treated at National Cancer Institute (NCI), Cairo University were investigated. Formalin? fixed, paraffin-embedded sections were analyzed for: 1) bcl-2 gene rearrangement including major break point region (mbr) and minor cluster region (mcr) by polymerase chain reaction (PCR), and 2) bcl-2 protein expression by immunohistochemistry using Dako 124 clone. Results were correlated with the clinical features and subsequent clinical course.

RESULTS

Bcl-2 gene rearrangement was detected in 8 cases (20%), 2 cases at mbr, and 6 cases at mcr. Bcl-2 protein (>10%) was expressed in 24 cases (60%), irrespective of the presence of t(14;18) translocation. The t(14;18), and bcl-2 protein overexpression were more frequently associated with failure to achieve a complete response to therapy (p=0.008, and 0.04, respectively). DLBCL patients with t(14;18), and bcl-2 protein expression had a significantly reduced 5-year disease free survival (p=0.04, and 0.01, respectively).

CONCLUSION

The t(14;18) translocation, and bcl-2 protein expression define a group of DLBCL patients with a poor prognosis, and could be used to tailor treatment, and to identify candidates for therapeutic approaches. Geographic differences in t(14;18) may be related to the difference in distribution of bcl-2 breakpoints.

摘要

背景

弥漫性大B细胞淋巴瘤（DLBCL）是最常见的非霍奇金淋巴瘤（NHL）类型。尽管联合化疗改善了治疗结果，但目前所有患者中约50%有望实现长期治愈，因此特别需要寻找能够识别高危患者的参数。初发性DLBCL中bcl-2基因重排的存在提示可能起源于滤泡中心细胞，或许具有独特的临床行为。本研究调查了一组接受统一评估和治疗的初发性结内DLBCL患者中t(14;18)易位和bcl-2蛋白过表达的频率及预后意义。

材料与方法

对开罗大学国家癌症研究所治疗的40例初发性结内DLBCL患者进行了研究。对福尔马林固定、石蜡包埋切片进行如下分析：1）通过聚合酶链反应（PCR）检测bcl-2基因重排，包括主要断裂点区域（mbr）和次要簇区域（mcr）；2）使用Dako 124克隆通过免疫组织化学检测bcl-2蛋白表达。将结果与临床特征及后续临床病程进行关联分析。

结果

8例（20%）检测到bcl-2基因重排，2例位于mbr，6例位于mcr。24例（60%）表达bcl-2蛋白（>10%），无论是否存在t(14;18)易位。t(14;18)和bcl-2蛋白过表达更常与治疗未达到完全缓解相关（分别为p=0.008和0.04）。存在t(14;18)和bcl-2蛋白表达的DLBCL患者5年无病生存率显著降低（分别为p=0.04和0.01）。