摘要目的 探讨间期荧光原位杂交( FISH)技术对B细胞淋巴瘤诊断、鉴别诊断、预后评估及治疗指导的应用价值.方法 收集四川大学华西医院2010年5月至2016年12月间期FISH检测的B细胞淋巴瘤604例,对其分子遗传学特征,包括 MYC、bcl-2、bcl-6、IRF4、MYC/IgH、bcl-2/IgH、CCND1/IgH、IgH、API2/MALT1、p53/ATM、D13S319/CEP12基因的状态分析.结果 604例患者男性61. 6%(372/604),女性38. 4%(232/604),平均年龄47. 7岁(2～90岁).包括大B细胞淋巴瘤463例和小B细胞淋巴瘤141例.间期FISH检测总体阳性率为59. 8%(361/604). 463例大B细胞淋巴瘤中检出12. 5%(58/463) MYC易位;9. 5%(44/463) bcl-6易位;2. 2%(10/463) bcl-2易位. (1)弥漫性大B细胞淋巴瘤363例,Hans分型包括生发中心B细胞( GCB)型38. 6%(140/363)、非GCB型61. 4%(223/363). GCB型和非GCB型分别检出45. 7%(64/140)和21. 5%(48/223)基因异常,差异具有统计学意义(P＝0. 001). MYC、bcl-2易位更易见于 GCB 型. (2)11 例(2. 4%,11/463)伴有MYC和bcl-2或bcl-6重排高级别B细胞淋巴瘤(双重打击淋巴瘤);1例(0. 2%,1/463)伴有MYC、bcl-2和bcl-6重排高级别 B细胞淋巴瘤(三打击淋巴瘤);2 例( 0. 4%,2/463) bcl-6和 bcl-2易位.(3)Burkitt 淋巴瘤 86 例, 94. 2%( 81/86)检出 MYC 易位, 83. 7%( 72/86)检出 MYC/IgH 融合.(4)2例IRF4+大B细胞淋巴瘤检出IRF4基因分离. 141例小B细胞淋巴瘤中包括滤泡淋巴瘤19例、套细胞淋巴瘤29例、黏膜相关淋巴组织结外边缘区淋巴瘤39例、慢性淋巴细胞白血病/小淋巴细胞淋巴瘤54例,其相应的遗传学改变检出比例分别为9/19、100%(29/29)、30. 8%(12/39)和68. 5%(37/54).结论 间期FISH技术能快速准确检测B细胞淋巴瘤的基因状态.检测出的不同遗传学改变对B细胞淋巴瘤不同亚型的诊断、鉴别诊断、预后评估及治疗指导方面具有特异性检测意义.

abstractsObjective To investigate the feasibility and value of interphase fluorescence in situ hybridization ( FISH) in the pathological diagnosis, differential diagnosis and therapeutic assessment of B-cell lymphomas. Methods The cohort included 604 cases of B-cell lymphoma which were collected at West China Hospital from May 2010 to December 2016.And all were subjected to interphase FISH using 11 break apart or fusion probes ( MYC, bcl-2, bcl-6, IRF4, MYC/IgH, bcl-2/IgH, CCND1/IgH, IgH, API2/MALT1, p53/ATM, and D13S319/CEP12) . Results The median age of the 604 B-cell lymphoma patients was 47. 7 (aged 2-90) years including 372 men and 232 women. All the cases was divided into 463 large B cell lymphomas(LBL) and 141 small B cell lymphomas, and the total interphase FISH positive rate was 59. 8%(361/604). Among the 463 LBL, 12. 5%(58/463), 9. 5%(44/463) and 2. 2%(10/463) of cases showed MYC, bcl-6 and bcl-2 gene rearrangements respectively; and 363 diffuse large B cell lymphoma (DLBCLs) were reclassified as germinal center B-cell (GCB) subtype (38. 6%, 140/363) and non-GCB subtype (61. 4%, 223/363) by Hans algorithm. The rearrangement rates in GCB and non-GCB DLBCL were 45. 7%(64/140)and 21. 5%(48/223;P＝0. 001), respectively. Compared to the non-GCB DLBCL, GCB DLBCL showed higher MYC and bcl-2 gene rearrangements ( P＝0. 001) . Eleven ( 2. 4%, 11/463) cases had MYC and bcl-6 or bcl-2 gene rearrangement ( double-hit lymphoma); one ( 0. 2%, 1/463) case had MYC,bcl-6 and bcl-2 gene rearrangements (triple-hit lymphoma); two (0. 4%,2/463) cases had bcl-2 and bcl-6 gene rearrangements. MYC translocation and MYC/IgH fusion were detected in 94. 2%(81/86) and 83. 7%(72/86) cases of Burkitt lymphomas. IRF4 rearrangement was detected in two cases of IRF4+LBCL. Genetic abnormalities were detected in 9/19, 100%(29/29), 30. 8%(12/39) and 68. 5%( 37/54 ) cases of follicular lymphoma, mantle cell lymphoma, MALT lymphoma and chronic lymphocytic leukemia, respectively. Conclusions Interphase FISH can rapidly and accurately detect the genetic changes in B-cell lymphomas. Different genetic changes are specifically valuable to the diagnosis, differential diagnosis, prognosis evaluation and treatment guidance of various B-cell lymphomas.