BCL-6、MYC和p53基因异常与弥漫性大B细胞淋巴瘤免疫学亚型及预后的关系

Correlation of BCL-6, MYC and p53 gene abnormalities with immunological subtypes and prognosis of diffuse large B-cell lymphoma

目的探讨弥漫性大B细胞淋巴瘤（diffuselargeB-celllymphoma，DLBCL）患者BCL-6、MYC和p53基因的异常情况，用并分析它们与免疫学亚型及预后的关系。方法应用间期荧光原位杂交技术分析46例DLBCL患者BCL-6、Myc和p53基因的异常情况，用免疫组织化学技术（Envision法）对DLBCL进行CD3、CD10、CD20、BCL-6、MUM-1、BCL-2和Ki-67标记，根据Hans的分类方法将其分为生发中心B细胞型（germinalcenterBcell，GCB型）和非生发中心B细胞型（non—germinalcenterBcell，non-GCB型）。结果46例患者中，BCL-6基因重排10例，BCL-6重排与BCL-6蛋白的表达两者之间差异无统计学意义（P=0．245）。BCL-6基因重排与DLBCL患者的总生存时间（P=0．138）和无进展生存时间（P=0．095）无统计学相关性。MYC重排4例，全部见于GCB型。p53基因缺失14例，p53基因缺失组与p53基因正常组相比，生存时间差异有统计学意义（总生存时间：P=0．046；无进展生存时间：P=0．043）。结论间期荧光原位杂交技术可以快速、准确、灵敏的检测BCL-6、MYC和p53基因的异常。BCL-6基因重排与BCL-6蛋白的表达之间无统计学相关性。MYC重排多见于GCB亚型组，p53基因缺失的患者预后较差。p53基因可以作为判断DLBCL预后的参考指标。

Objective To investigate BCL-6, MYC and p53 genes abnormalities in diffuse large B-cell lymphoma （DLBCL） and correlate the result with immunosubtypes and prognosis. Methods Interphase fluorescence in situ hybridization （I-FISH） was performed to detect the BCL-6, MYC and p53 genes. Immunohistochemistry （Envision method） was used to measure the expressions of CD3, CD10, CD20, BCL-6, MUM-1, BCL-2 and Ki-67 genes in DLBCL. The patients were classified into germinal center B cell-like （GCB） and non-GCB subtypes according to Hans＇ algorithm. Results BCL-6 rearrangement was detected in 10 of 46 DLBCL cases. The presence of gene rearrangement had no correlation with BCL-6 protein expression （P=0. 245）. Overall survival （OS, P=0. 138） and progression-free survival （PFS, P= 0. 095） were not influenced by BCL-6 rearrangement. All MYC rearrangements were detected in GCB type DLBCL. Deletion of p53 gene was detected in 14 cases and was significantly associated with shorter OS （P=0. 046） and PFS （P= 0. 043）. Conclusion I-FISH is a rapid, accurate and sensitive method for detecting BCL-6, MYC and p53 abnormalities. No correlation was found between BCL-6 gene rearrangement and BCL-6 protein expression. MYC translocation was more common in GCB type DLBCL compared with non-GCB type ones. Patients with p53 deletion had a poorer prognosis. The p53 gene may provide a useful indicator for the prognosis of DLBCL.