Mad2 overexpression is associated with high cell proliferation and reduced disease-free survival in primary gastrointestinal diffuse large B-cell lymphoma

作者：Chen, Fei^*; Liu, Shangqin; Zhou, Yi; Shen, Hui; Zuo, Xuelan

来源：Hematology, 2016, 21(7): 399-403.

DOI：10.1080/10245332.2015.1101970

• Primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL)
• Mitotic arrest deficiency protein 2 (Mad2)
• Nuclear associated antigen (Ki-67)
• B-cell lymphoma-6 gene (BCL-6)

Objectives: 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. @@@ Methods: 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. @@@ Results: 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). @@@ Conclusions: 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.

• 出版日期2016
• 单位武汉大学