Chen Fei, Liu Shangqin, Zhou Yi, Shen Hui, Zuo Xuelan
a Department of Hematology , Zhongnan Hospital of Wuhan University , 169 Dong Hu Road, Wuhan 430071 , China.
Hematology. 2016 Aug;21(7):399-403. doi: 10.1080/10245332.2015.1101970. Epub 2016 Mar 16.
Primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) is a rare hematological malignancy with limited results on carcinogenesis and clinical characteristics. The aims of the current study were to examine mitotic arrest deficiency protein 2 (Mad2) expressions in PGI-DLBCL, and assess its association with Ki-67 expression, Helicobacter pylori (H. pylori) infection, BCL-6 gene rearrangement, and clinicopathological variables.
Cancer tissues from 38 PGI-DLBCL patients were examined for Mad2, Ki-67, and H. pylori expression by immunohistochemistry, using normal gastrointestinal tissues and nodal DLBCL as controls. BCL-6 gene translocation was analyzed by fluorescence in situ hybridization (FISH), and Mad2 expression status was evaluated along with clinicopathological characteristics.
Mad2 expression was increased in PGI-DLBCL patients when compared with controls. The expression of Mad2 was 51.55 ± 22.88% in PGI-DLBCL, which was higher than reactive lymph node (28.77 ± 10.89%) and lymphoid nodule in normal gastrointestinal tissue (26.41 ± 11.30%) (P = 0.002), while it was comparable to nodal DLBCL (57.23 ± 20.79%) (P = 0.358). Mad2 overexpression had a positive correlation with Ki-67 proliferation index (r = 0.55, P = 0.01) in PGI-DLBCL, and patients with BCL-6 gene rearrangement had lower Mad2 expression (P = 0.032) than patients with intact BCL-6, while no relation was found between Mad2 expression and H. pylori infection. PGI-DLBCL patients with higher Mad2 expression had lower estimated disease-free survival (DFS) (17.10% vs. 53.00%) (P = 0.049). However, no correlation was found between Mad2 expression levels and overall survival (OS) (P = 0.443).
Aberrant Mad2 expression was associated with cell proliferation and genetic instability, which may contribute to the carcinogenesis of PGI-DLBCL. Mad2 overexpression indicated a poor DFS and may be a potential biomarker for estimating prognosis for PGI-DLBCL patients.
原发性胃肠道弥漫性大B细胞淋巴瘤（PGI-DLBCL）是一种罕见的血液系统恶性肿瘤，其致癌机制和临床特征相关研究结果有限。本研究旨在检测PGI-DLBCL中纺锤体装配检查点蛋白2（Mad2）的表达情况，并评估其与Ki-67表达、幽门螺杆菌（H. pylori）感染、BCL-6基因重排及临床病理变量之间的关系。
采用免疫组织化学法检测38例PGI-DLBCL患者癌组织中Mad2、Ki-67及H. pylori的表达，以正常胃肠道组织和淋巴结DLBCL作为对照。采用荧光原位杂交（FISH）技术分析BCL-6基因易位情况，并结合临床病理特征评估Mad2表达状态。
与对照组相比，PGI-DLBCL患者中Mad2表达升高。PGI-DLBCL中Mad2的表达为51.55±22.88%，高于反应性淋巴结（28.77±10.89%）和正常胃肠道组织中的淋巴小结（26.41±11.30%）（P = 0.002），但与淋巴结DLBCL（57.23±20.79%）相当（P = 0.358）。在PGI-DLBCL中，Mad2过表达与Ki-67增殖指数呈正相关（r = 0.55，P = 0.01），BCL-6基因重排的患者Mad2表达低于BCL-6完整的患者（P = 0.032），而Mad2表达与H. pylori感染无关。Mad2表达较高的PGI-DLBCL患者无病生存率（DFS）较低（17.10% 对53.00%）（P = 0.049）。然而，未发现Mad2表达水平与总生存率（OS）之间存在相关性（P = 0.443）。
Mad2表达异常与细胞增殖和遗传不稳定有关，可能参与PGI-DLBCL的致癌过程。Mad2过表达提示DFS较差，可能是评估PGI-DLBCL患者预后的潜在生物标志物。
