摘要目的 利用荧光原位杂交(FISH)技术观察间变性大细胞淋巴瘤(ALCL)中间变性淋巴瘤激酶(ALK)基因相关染色体易位,探讨其在临床病理学中的应用价值.方法 收集复旦大学附属肿瘤医院和上海交通大学附属新华医院病理科1999至2006年间病例55例(其中45例ALCL,10例淋巴结反应性增生),以LSI ALK双色分离重排探针,利用FISH法检测ALCL中ALK相关染色体易位,并与前期免疫组织化学(IHC)、逆转录聚合酶链反应(RT-PCR)检测结果进行对比分析.结果 FISH检测结果显示,45例ALCL中,38例成功检测到清晰的红绿信号,其中24例(24/38,63.2％)见明显的荧光分离信号,表明存在ALK相关染色体易位,其中1例表现为ALK基因多拷贝;14例(36.8％,14/38)仅见红绿融合荧光信号,表明不存在ALK相关染色体易位;7例无荧光信号或信号太弱无法判断结果,检测失败.FISH法检测AI.K相关染色体易位与前期IHC检测AIK蛋白、RT-PCR法检测ALK相关融合基因的结果基本一致(均P＜0.01),10例淋巴结反应性增生病例中,均未见ALK相关染色体易位.结论 ALCL是一类具有特殊临床表现、病理形态及ALK表达异常的淋巴瘤.FISH法能有效地检测出ALCL中ALK相关染色体易位,但其可能受蜡块存放时间影响较大,与IHC、RT-PCR法互相补充,有助于ALK+ ALCL与ALK ALCL的鉴别诊断.

abstractsObjective To investigate clinicopathologic features and clinical value of the chromosonal translocation involving anaplastic lymphoma kinase (ALK) in anaplastic large cell lymphoma (ALCL) by fluorescence in situ hybridization (FISH).Methods A total of 55 cases,including45 cases of ALCL and 10 reactive lymphoid hyperplasia,were collected during 1999 to 2006 in the Department of Pathology,Fudan University Shanghai Cancer Center,and Xinhua Hospital Affiliated to Shanghai Jiaotong University.All cases were studied by FISH using dual color break apart probes of ALK for detection of chromosomal translocation,compared with the previous results of immunohistochemistry (IHC) and reversetranscriptase polymerase chain reaction ( RT-PCR ) for the detection of ALK aberrations.Results The resuh of FISH showed that the clear red and green fluorescence signals were detected in 38 cases of ALCL,in which conspicuous split signals were observed in tumor cells in 24 cases ( 63.2％ ),suggesting the rearrangement of the ALK locus,with multiple copies of ALK gene in one case.In addition,the rearrangement of the ALK locus was not identified in 14 of 38 cases ( 36.8％ ) ; and the FISH results were unable to be evaluated in 7 cases,because no fluorescent signals involving ALK gene were found or signals were too weak to be analyzed.The concordance for the detection ALK aberrations in ALCL between FISH and RT-PCR,FISH and IHC were both statistically significant ( P ＜ 0.01 ).Chromosomal translocation involving ALK gene was not found in all 10 cases of reactive lymphoid hyperplasia.Conclusions ALCL is an entity of lymphoma characterized by special clinical presentation,morphology,and ALK aberrations.FISH is helpful for detection of the chromosomal translocations involving ALK in ALCL,however,the detection efficiency by FISH may be affected by storage time of the parafin-embedded tissue; and therefore combined detection with IHC and RT-PCR could complement each other and help for differential diagnosis of ALK + ALCL from ALK- ALCL.