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

Abstract

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.

Keywords:

• 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)

Disclaimer statements

Contributors All authors have contributed to this work.

Funding This work was supported by grants from the Natural Science Foundation of Hubei Province (2013CFB266) (F.C).

Conflicts of interest There are no conflicts of interest regarding this paper.

Ethics approval The institutional review board of Zhongnan Hospital of Wuhan University has approved this study.