bcl-2与bcl-6在弥漫性大B细胞淋巴瘤中表达的研究

Study of the expression of bcl-2 and bcl-6 in diffuse large B-cell lymphoma

目的从蛋白水平和基因水平研究bcl-2、bcl-6在弥漫性大B细胞淋巴瘤（DLBCL）的表达。方法应用免疫组织化学EnVision法对73例DLBCL进行CD3、CD10、CD20、bcl-2、bcl-6、MUM-1的标记。应用荧光原位杂交（FISH）技术检测其中57例t（14；18）染色体异位bcl-2基因的异常情况和54例bcl-6基因所在的3q27染色体的断裂和扩增情况。结果肿瘤细胞表达CD10、bcl-6、MUM-1、bcl-2的阳性率分别为15．1％、38．4％、71．2％、79．2％。57例患者中16例（28．1％）存在t（14；18）。bcl-2蛋白表达与免疫学亚型有相关性（P=0．035），t（14；18）与预后有相关性（P=0．045），t（14；18）与bcl-2蛋白表达无相关性（P=0．710）。54例中3q27染色体断裂11例（20．4％），扩增14例（25．9％）。bcl-6阳性表达较阴性者预后好（P=0．041）。bcl-6与3q27断裂和扩增无相关性（均P=1．000）。结论bcl-2、bcl-6蛋白和基因表达是各自独立的事件，它们在DLBCL中的意义不同。bcl一2蛋白是与免疫学亚型相关的预后标志物，bcl-2阳性的GCB型预后较差；t（14；18）是独立预后事件，阳性者预后较差，对靶向治疗患者应检测t（14；18）；bcl-6蛋白的表达有助于DLBCL的预后判断，可作为独立的预后因子。3q27染色体断裂可能提示预后较差。

Objective To investigate the protein and gene expression of bcl-2, bcl-6 in diffuse large B-cell lymphoma （DLBCL）. Methods 73 cases of DLBCL were selected for study using the Envision immunohistochemistry method with a panel of antibodies CD3, CD10, CD20, bcl-6, bcl-2, MUM-1. The bcl-2 gene expression in 57 of 73 cases with chromosome translocation t （14; 18）, breakage and amplification of 3q27 chromosome in 54 of 73 cases were detected by fluorescence in situ hybridization （FISH） method. Results The percentages of tumor cells expressing CDj0, bcl-6, MUM-1, bcl-2 were separately 15.1%, 38.4 fro, 71.2 %, 79.2 % . t （14;18） chromosomes were detected in 16 of 57 eases （28.1%）. The expression of bcl-2 protein have significantly correlated with immunophenotype subtype （P =0.035）, and t （14;18） was significantly correlated with the prognosis （P =0.045）. There were no association between the expression of bcl-2 protein and t （14;18）（P =0.710）. 11 of 54 eases were presented with 3q27 chromosomal breakage （20.4 %）, and 14 cases were chromosomal amplification （25.9 %）. The prognosis of cases with positive bcl-6 protein was better than that with negative protein obviously. There was no relationship between bcl-6 and 3q27 chromosomal breakage or amplification （P =1.000）. Conclusion The expression of bcl-2, bcl-6 protein and gene were different events and had the different significance on DLBCL. The expression of bcl-2 protein was a prognostic marker correlated with immunophenotype subtype, and GCB type with the positive expression of bcl-2 protein had the poor prognosis. Conversely, t（14;18） was an independent event for the prognosis, and the positive expression have the poor prognosis. Patients who require the target therapy should be detected for the t（14;18）. The expression of bcl-6 protein was beneficial to the judgment of DLBCL prognosis, it could be an independent factor of the prognosis. 3q27 chromosomal breakage may be a hint to the poor prognosis.