Zeng Li-ping, Wen Yi-lei, Ma Yun, Wang Gui-qiu, Li Ying, Wang Jin, Xu Li-li, Zhang Xue-mei
Department of Pathology, Guangxi Medical University, Nanning, China.
Zhonghua Bing Li Xue Za Zhi. 2011 Jun;40(6):377-81.
To evaluate the molecular mechanism and prognostication of bcl-2 protein expression in different subgroups of diffuse large B-cell lymphoma(DLBCL) in Guangxi Zhuang Autonomous Region, China.
Immunohistochemical stains for CD10, bcl-6, MUM-1, bcl-2 and NF-κB were performed in 214 cases of DLBCL. The Hans immunologic classification was applied to classify DLBCL into GCB and non-GCB subgroups. Using a dual-probe fluorescence in-situ hybridization (FISH) assay, IgH/bcl-2 gene translocation and bcl-2 amplification were analyzed.
In 214 cases of DLBCL, 30.8% (66/214) of cases were GCB and 69.2% (148/214) were non-GCB. Twenty-seven point three percent (18/66) of GCB subgroups and 59.5% (88/148) of non-GCB subgroups had bcl-2 protein expression, with a significant difference (P < 0.01). IgH/bcl-2 translocation was positive in 3.7% (8/214) of cases, even majority of them (6/8) was found in GCB subgroup, while represented only 9.1% of GCB case. There was a significant difference (P = 0.02) in bcl-2 gene amplification between GCB (27/66, 40.9%) and non-GCB subgroup (86/148, 58.1%). Among non-GCB cases, the expression of bcl-2 was correlated with that of NF-κB expression and bcl-2 gene amplification (r = 0.216 and 0.219, respectively, P < 0.05). No similar correlation was observed in GCB cases. The overall survival time of bcl-2-positive patients (31.4 ± 3.8) months was shorter than that of bcl-2-negative patients (40.2 ± 4.2) months. In conjunction with immunophenotypes and clinical stages, the bcl-2 positive patients had a 1.89 times higher risk than that of the bcl-2 negative patients.
Majority of the cases were prognostically unfavorable non-GCB subgroups among DLBCL, which were characterized by high frequency of bcl-2 gene amplification and low frequency of IgH/bcl-2 translocation. The anti-apoptotic gene bcl-2 was frequently expressed in non-GCB subgroups and closely related to the gene amplification and NF-κB activation. bcl-2 positive patients had more short overall survival times, would face significant higher risk of death, these results suggested that bcl-2 could be a prognostic marker independent to clinical staging and immunophenotyping.
评估中国广西壮族自治区弥漫性大B细胞淋巴瘤（DLBCL）不同亚组中bcl-2蛋白表达的分子机制及预后价值。
对214例DLBCL患者进行CD10、bcl-6、MUM-1、bcl-2和NF-κB的免疫组织化学染色。采用汉斯免疫分类法将DLBCL分为生发中心B细胞（GCB）和非生发中心B细胞（non-GCB）亚组。使用双探针荧光原位杂交（FISH）检测分析IgH/bcl-2基因易位和bcl-2基因扩增情况。
214例DLBCL患者中，GCB亚组占30.8%（66/214），non-GCB亚组占69.2%（148/214）。GCB亚组中27.3%（18/66）和non-GCB亚组中59.5%（88/148）有bcl-2蛋白表达，差异有统计学意义（P<0.01）。IgH/bcl-2易位阳性率为3.7%（8/214），其中大部分（6/8）见于GCB亚组，但仅占GCB病例的9.1%。GCB亚组（27/66，40.9%）和non-GCB亚组（86/148，58.1%）的bcl-2基因扩增差异有统计学意义（P = 0.02）。在non-GCB病例中，bcl-2表达与NF-κB表达及bcl-2基因扩增相关（r分别为0.216和0.219，P<0.05）。GCB病例中未观察到类似相关性。bcl-2阳性患者的总生存时间（31.4±3.8）个月短于bcl-2阴性患者（40.2±4.2）个月。结合免疫表型和临床分期分析，bcl-2阳性患者的死亡风险是bcl-2阴性患者的1.89倍。
DLBCL患者中多数为预后不良的non-GCB亚组，其特征为bcl-2基因扩增频率高和IgH/bcl-2易位频率低。抗凋亡基因bcl-2在non-GCB亚组中频繁表达，且与基因扩增和NF-κB激活密切相关。bcl-2阳性患者总生存时间较短，死亡风险显著更高，提示bcl-2可能是独立于临床分期和免疫表型的预后标志物。
