Objective: 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.
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。.
Keywords: Gene fusion; In situ hybridization, fluorescence; Lymphoma, B-cell; Translocation, genetic.