90例弥漫性大B细胞淋巴瘤的分子遗传学及预后意义初探

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目的:分析90例弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)的临床病理学特征及其临床意义。方法:收集90例DLBCL石蜡包埋组织标本及预后资料,采用免疫组织化学技术及间期荧光原位杂交(Fluorescence in situ Hybridization,FISH)技术研究其免疫表型和分子遗传学特征。结果:本组病例中,70例原发于淋巴结外,20例原发于淋巴结。根据Hans模型,42.2%(38/90)的DLBCL起源于生发中心B细胞(GC),57.8%(52/90)起源于非生发中心B细胞(Non-GC)。IGH、bcl-6、bcl-2及c-myc基因易位的阳性率分别为33.3%(30/90)、22.2%(20/90)、4.4%(4/90)和3.3%(3/90);bcl-2、bcl-6、c-myc及IGH基因多拷贝的阳性率分别为51.1%(46/90),40%(36/90)、30%(27/90)和14.4%(13/90)。20例bcl-6基因易位的DLBCL中,14例为Non-GC起源,6例为GC起源;4例bcl-2基因易位的病例中,3例为GC起源,1例为Non-GC起源;3例c-myc基因易位的病例中,2例为GC起源,1例为Non-GC起源。结外DLBCL的IGH基因易位的阳性率高于结内者(P<0.05);结内DLBCL的c-myc基因多拷贝的阳性率高于结外者(P<0.05)。本组29例有随访结果的病例显示,IGH、bcl-6、bcl-2及c-myc基因易位及多拷贝与预后无明显相关(P>0.05)。结论:本组DLBCL总的分子遗传学异常率(包括因易位及拷贝数的异常)为82.2%,其中以bcl2多拷贝(51.1%)最为多见。不存在IGH、bcl-6、bcl-2及c-myc基因异常,不能除外DLBCL的诊断。少部分DLBCL中存在Burrkitt淋巴瘤特征性的c-myc基因易位。IGH、bcl-2、bcl-6及c-myc基因易位及拷贝数的异常在DLBCL中不具有的预后判定意义。 Objective: To analyze the clinicopathological features and clinical significance of 90 cases of diffuse large B-cell lymphoma (DLBCL). Methods: Ninety cases of DLBCL paraffin-embedded tissue samples and prognostic data were collected. The immunophenotypic and molecular genetic characteristics were studied by immunohistochemistry and fluorescence in situ hybridization (FISH). Results: In this group of cases, 70 cases of primary in the lymph nodes, 20 cases of primary lymph nodes. According to the Hans model, 42.2% (38/90) of DLBCL originated in germinal center B cells (GC) and 57.8% (52/90) originated in non-GC. The positive rates of IGH, bcl-6, bcl-2 and c-myc translocation were 33.3% (30/90), 22.2% (20/90), 4.4% (4/90) and 3.3% The positive rates of multiple copies of bcl-2, bcl-6, c-myc and IGH genes were 51.1% (46/90), 40% (36/90), 30% (27/90) and 14.4% (13/90). Among 20 cases of bcl-6 translocated DLBCL, 14 cases were Non-GC origin and 6 cases were GC origin. Of the 4 cases with bcl-2 gene translocation, 3 cases were GC origin and 1 case was Non-GC Of the three c-myc translocations, two were GC origin and one was Non-GC origin. The positive rate of IGH gene translocation in extra-node DLBCL was higher than that in node (P <0.05). The positive rate of multiple copies of c-myc gene in DLBCL was higher than that in extranodal (P <0.05). The follow-up results of 29 cases in this group showed that the translocation and multicopy of IGH, bcl-6, bcl-2 and c-myc genes had no significant correlation with prognosis (P> 0.05). Conclusion: The total abnormal rate of molecular genetics of DLBCL in this group (including the abnormality due to translocation and copy number) was 82.2%, of which the most common was bcl2 multi-copy (51.1%). Absence of IGH, bcl-6, bcl-2 and c-myc gene abnormalities, can not exclude the diagnosis of DLBCL. A small number of DLBCL Burckitt lymphoma characteristic c-myc gene translocation. The prognostic significance of abnormalities of IGH, bcl-2, bcl-6 and c-myc translocation and copy number in DLBCL.
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