bcl-2／IgH基因易位及免疫球蛋白基因重排在滤泡性淋巴瘤中的应用

Detection and application of bcl.2/IgH gene translocation and immunoglobulin gene rearrangement in follicular lymphoma

目的探讨bcl－2/IgH基因易位及免疫球蛋白（Ig）H/L基因重排检测在滤泡性淋巴瘤（FL）不同分级中的应用。方法应用荧光原位杂交（FISH）法检测了广东省人民医院病理科2014年9月至2016年12月收集的32例FL bcl－2/IgH基因易位状态，同时应用聚合酶链反应（PCR）－GeneScan法检测了32例FL免疫球蛋白重链/轻链（IgH/L）基因重排，统计分析bcl－2/IgH基因易位状态与肿瘤分级、克隆性IgH/L基因重排的关系。结果32例FL石蜡标本，bcl－2/IgH基因易位17例，其中，FL1、FL2易位的发生比例分别为12/13、3/5，而FL3易位的发生比例仅为2/14；24例IgH/L基因重排阳性，其中，FL1基因重排的检出比例为7/13，FL2、FL3重排的检出比例分别为4/5、13/14。Spearman等级相关检验和χ^2检验结果显示，bcl－2/IgH基因易位与FL的分级存在显著负相关关系（rp＝－0.661），bcl－2/IgH基因易位率随着肿瘤分级的增加而降低，FL1、2和FL3中表达差异有统计学意义（P〈0.05）；而IgH/L基因重排在FL3中的检测率高于FL1、2，有效地弥补了单纯FISH检测bcl－2/IgH基因易位的缺陷。结论联合FISH和PCR－GeneScan检测提高了FL分子诊断的阳性率，比单纯FISH检测染色体异常或单纯重排检测更灵敏，为FL疑难病例的诊断和鉴别诊断提供了更加准确和客观的科学依据。

ObjectiveTo evaluate the application of FISH testing of bcl-2/IgH gene translocation and IgH/L gene rearrangement in different stages of follicular lymphoma.MethodsIn 32 follicular lymphoma cases, which were collected at Guangdong General Hospital from September 2014 to December 2016, the bcl-2/IgH gene ectopic state was detected by FISH while the IgH/L gene rearrangement was tested using PCR-GeneScan to analyze the relationship between bcl-2/IgH gene translocation, different stages of follicular lymphoma and clonal immunoglobulin （IgH/L） gene rearrangements.ResultsFrom the paraffin sections of all 32 follicular lymphomas, 17 cases showed bcl-2/IgH gene translocation, and the percentages of FL1, FL2 and FL3 translocation were 12/13, 3/5 and 2/14, respectively. Among the 24 cases of IgH/L gene arrangements identified from the total sample, the occurrence rates of FL1, FL2 and FL3 gene arrangement were 7/13, 4/5 and 13/14, respectively. Spearman′s rank correlation analysis and χ^2 analysis showed that bcl-2/IgH gene translocation was negatively correlated with follicular lymphoma stage and the association was statistically significant. In more advanced stages of follicular lymphoma, the occurrence of bcl-2/IgH gene translocation tended to decrease with distinct FL1, FL2 and Fl3 gene expression （P〈0.05）. As IgH/L gene rearrangement in FL3 was higher than that in FL1 and FL2, its detection may be complimentary to FISH test for bcl-2/IgH gene translocation in diagnosing follicular lymphoma.ConclusionsThe combined use of FISH and PCR-GeneScan increases the positive rate of follicular lymphoma diagnosis, and this combination is more sensitive than FISH or clonal analysis only to detect the chromosomal abnormality or the gene rearrangement.