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高水平的bcl-2蛋白表达与基因异常无关,但可预测淋巴细胞性淋巴瘤患者的预后较差。

High levels of bcl-2 protein expression do not correlate with genetic abnormalities but predict worse prognosis in patients with lymphoblastic lymphoma.

作者信息

Gu Yajun, Pan Yi, Meng Bin, Guan Bingxin, Fu Kai, Sun Baocun, Zheng Fang

机构信息

Department of Clinical Immunology, School of Medical Laboratory, Tianjin Medical University, Tianjin, 300203, China.

出版信息

Tumour Biol. 2013 Jun;34(3):1441-50. doi: 10.1007/s13277-013-0647-9. Epub 2013 Mar 14.

DOI:10.1007/s13277-013-0647-9
PMID:23494176
Abstract

We aimed to investigate bcl-2, bcl-6, and c-myc rearrangements in patients with lymphoblastic lymphoma (LBL), especially focus on the correlation of protein expression with genetic abnormalities. Moreover, their prognostic significance was further analyzed in LBL. Protein expression and genetic abnormalities of bcl-2, bcl-6, and c-myc were investigated in microarrayed tumors from 33 cases of T cell LBL and eight cases of B cell lineage. Immunohistochemical (IHC) staining was performed to evaluate protein expression, including bcl-2, bcl-6, c-myc, TdT, CD1α, CD34, Ki-67, PAX-5, CD2, CD3, CD4, CD8, and CD20. Genetic abnormalities of bcl-2, bcl-6, and c-myc were detected by dual color fluorescence in situ hybridization (FISH). Bcl-2 protein was positive in 51.2 % (21/41) of the patients, bcl-6 protein in 7.3 % (three out of 41), and c-myc protein in 78.0 % (32/41). Bcl-2 breakpoint was found in two cases by FISH analysis. There was no evidence of bcl-6 or c-myc rearrangement in patients with LBL. However, both gene gain and loss events occurred in bcl-2, bcl-6, and c-myc. A univariate analysis showed that stage III or IV, elevated lactate dehydrogenase (LDH), and positivity for bcl-2 protein were associated with shorter survival (p<0.05). Enhanced protein expression and detectable genetic abnormalities of bcl-2, bcl-6, and c-myc were observed in patients with LBL. No statistical correlation was found between IHC results and cytogenetic findings. Stage III or IV, elevated LDH, and positivity for bcl-2 protein were identified as adverse prognostic factors. The patients with more adverse factors would have increasingly worse prognosis.

摘要

我们旨在研究淋巴细胞淋巴瘤(LBL)患者中bcl-2、bcl-6和c-myc重排情况,尤其关注蛋白表达与基因异常之间的相关性。此外,还对它们在LBL中的预后意义进行了进一步分析。我们研究了33例T细胞LBL和8例B细胞系微阵列肿瘤中bcl-2、bcl-6和c-myc的蛋白表达及基因异常情况。采用免疫组织化学(IHC)染色评估蛋白表达,包括bcl-2、bcl-6、c-myc、TdT、CD1α、CD34、Ki-67、PAX-5、CD2、CD3、CD4、CD8和CD20。通过双色荧光原位杂交(FISH)检测bcl-2、bcl-6和c-myc的基因异常。bcl-2蛋白在51.2%(21/41)的患者中呈阳性,bcl-6蛋白在7.3%(41例中的3例)呈阳性,c-myc蛋白在78.0%(32/41)呈阳性。FISH分析发现2例存在bcl-2断点。LBL患者中未发现bcl-6或c-myc重排的证据。然而,bcl-2、bcl-6和c-myc均发生了基因增益和缺失事件。单因素分析显示,III期或IV期、乳酸脱氢酶(LDH)升高以及bcl-2蛋白阳性与生存期较短相关(p<0.05)。在LBL患者中观察到bcl-2、bcl-6和c-myc的蛋白表达增强及可检测到的基因异常。未发现IHC结果与细胞遗传学结果之间存在统计学相关性。III期或IV期、LDH升高以及bcl-2蛋白阳性被确定为不良预后因素。不良因素越多的患者预后越差。

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