Akkaya Bahar, Salim Ozan, Akkaya Hampar, Ozcan Mualla, Yucel Orhan Kemal, Erdem Ramazan, Iltar Utku, Undar Levent
Department of Pathology, Akdeniz University, Antalya, Turkey.
Indian J Pathol Microbiol. 2016 Jan-Mar;59(1):41-6. doi: 10.4103/0377-4929.178220.
Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma with marked biologic heterogeneity. MYC and BCL2 rearrangements have been reported in a proportion of DLBCLs, where they may be associated with an adverse clinical outcome. The aim of this study was to determine the frequency of MYC and BCL2 translocations in DLBCL and assess the prognostic impact in DLBCL patients.
In the present study, we evaluated the expression patterns of CD 10, BCL6, and MUM 1 by immunohistochemistry in 121 cases with DLBCL in tissue microarray (TMA): 62 cases in germinal center B-cells (GCBs); and 59 cases in activated B-cells (ABCs) of which 60 were females and 61 were males. MYC and BCL2 rearrangements were investigated by interphase fluorescence in situ hybridization on TMAs in 97 DLBCLs.
MYC rearrangements were observed in 11 of 97 cases. There was no association with other clinical features, including age, sex, and nodal/extranodal disease. MYC rearrangement was associated with significantly worse overall survival (P < 0.01). BCL2 rearrangements were observed in 14 of 97 cases. There was no association with other clinical features including age and sex. BCL2 rearrangement had a worse outcome (P < 0.01). MYC and BCL2 rearrangements were observed in 3 of 97 cases with the age of 53 (female), 53, 63 years old, respectively, died in 24, 18, and 35 months after the diagnosis. Two cases had primary nodal and one case primary extranodal presentations. All these patients had stage IV disease.
We concluded that C-MYC and BCL2 may contribute to aggressive transformation, and more mechanism-based therapy should be explored. Targeted therapies involving these rearrangements and its associated pathways may change the fate of DLBCLs. Analysis of MYC gene rearrangement along with BCL2 is critical in the identification of high-risk patients with poor prognosis.
弥漫性大B细胞淋巴瘤（DLBCL）是一种侵袭性非霍奇金淋巴瘤，具有显著的生物学异质性。在一部分DLBCL中已报道存在MYC和BCL2重排，它们可能与不良临床结局相关。本研究的目的是确定DLBCL中MYC和BCL2易位的频率，并评估其对DLBCL患者的预后影响。
在本研究中，我们通过免疫组织化学评估了121例组织芯片（TMA）中DLBCL患者的CD10、BCL6和MUM1表达模式：生发中心B细胞（GCB）62例；活化B细胞（ABC）59例，其中女性60例，男性61例。通过间期荧光原位杂交在97例DLBCL的TMA上研究MYC和BCL2重排。
97例中有11例观察到MYC重排。与其他临床特征无关，包括年龄、性别和淋巴结/结外病变。MYC重排与总体生存率显著较差相关（P<0.01）。97例中有14例观察到BCL2重排。与包括年龄和性别在内的其他临床特征无关。BCL2重排预后较差（P<0.01）。97例中有3例观察到MYC和BCL2重排，年龄分别为53岁（女性）、53岁和63岁，分别在诊断后24、18和35个月死亡。2例为原发性淋巴结病变，1例为原发性结外病变。所有这些患者均为IV期疾病。
我们得出结论，C-MYC和BCL2可能促成侵袭性转化，应探索更多基于机制的治疗方法。涉及这些重排及其相关途径的靶向治疗可能改变DLBCL的命运。分析MYC基因重排以及BCL2对于识别预后不良的高危患者至关重要。
