Jiang Hui-Yong, Li Hui-Ling, Hu Hai, He Ying, Zhao Tong
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Zhonghua Bing Li Xue Za Zhi. 2007 Feb;36(2):84-9.
To investigate the role of t (14; 18) chromosomal translocation and bcl-2 amplification in classification, clinical staging and prognostic evaluation of diffuse large B cell lymphoma (DLBCL).
Sixty cases of DLBCL were included in this investigation. Microdissection of the lymphoma tissue was performed. Tissue microarray and in-situ fluorescence hybridization technique were used to detect t (14; 18) and bcl-2 amplification. The phenotypes of either germinal center B-cell-like (GCB) or non-germinal center B-cell-like (non-GCB) were determined by immunohistochemistry including CD20, CD10, bcl-6 and MUM1 (S-P method) using the tissue microarray format. Clinical staging and therapeutic response were obtained by medical record review. The relationships among different parameters were analyzed by appropriate statistical methods.
Among 60 cases of DLBCL, bcl-2/IgH was positive in 10 cases and bcl-2 gene amplification was detected in 18 cases. Overall, 29 (48.3%) cases were GCB and 31 (51.7%) cases were non-GCB. The t (14; 18) was seen in 8 (80.0%) cases of GCB and 2 (20.0%) of non-GCB. The difference was statistical significance (P = 0.031). Over-expression of bcl-2 was seen in all cases having both t (14; 18) and bcl-2 gene amplification. Of thirty-six patients who underwent routine CHOP treatment, bcl-2 gene amplification was seen in 13 cases. In these cases, the rates of complete remission, partial remission and no change were 3 (23.1%), 4 (30.8%) and 6 (46.2%) respectively, and the clinical stages were stage I - II (1 case, 7.7%) and stage III - IV (12 cases, 92.3%). The clinical stages and therapeutic response were significantly different between the bcl-2 amplification cases and those without (P = 0.046 and P = 0.019, respectively).
T (14; 18) and/or bcl-2 gene amplification can lead to an over-expression of bcl-2 protein. The bcl-2 gene amplification correlates with worse therapeutic efficacies and advanced clinical stages. The reason for the correlation between bcl-2 over-expression and the prognosis is unclear, although it may be explained by different mechanisms that lead to bcl-2 over-expression. Detection of t (14; 18) chromosome translocation by FISH can be helpful in the classification of DLBCL.
探讨t（14；18）染色体易位及bcl-2基因扩增在弥漫性大B细胞淋巴瘤（DLBCL）分类、临床分期及预后评估中的作用。
本研究纳入60例DLBCL患者。对淋巴瘤组织进行显微切割。采用组织芯片和原位荧光杂交技术检测t（14；18）及bcl-2基因扩增情况。采用组织芯片形式，通过免疫组织化学（包括CD20、CD10、bcl-6和MUM1，S-P法）确定生发中心B细胞样（GCB）或非生发中心B细胞样（非GCB）表型。通过查阅病历获取临床分期及治疗反应情况。采用适当的统计学方法分析不同参数之间的关系。
60例DLBCL患者中，10例bcl-2/IgH阳性，18例检测到bcl-2基因扩增。总体而言，29例（48.3%）为GCB型，31例（51.7%）为非GCB型。t（14；18）在29例GCB型中的8例（80.0%）及31例非GCB型中的2例（20.0%）中出现。差异具有统计学意义（P = 0.031）。在同时存在t（14；18）和bcl-2基因扩增的所有病例中均观察到bcl-2过表达。36例行常规CHOP治疗的患者中，13例检测到bcl-2基因扩增。在这些病例中，完全缓解率、部分缓解率和无变化率分别为3例（23.1%）、4例（30.8%）和6例（46.2%），临床分期为Ⅰ-Ⅱ期（1例，7.7%）和Ⅲ-Ⅳ期（12例，92.3%）。bcl-2基因扩增病例与未扩增病例的临床分期及治疗反应存在显著差异（分别为P = 0.046和P = 0.019）。
t（14；18）和/或bcl-2基因扩增可导致bcl-2蛋白过表达。bcl-2基因扩增与较差的治疗效果及晚期临床分期相关。bcl-2过表达与预后之间相关性的原因尚不清楚，尽管可能由导致bcl-2过表达的不同机制来解释。通过荧光原位杂交检测t（14；18）染色体易位有助于DLBCL的分类。
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