title: Mad2 overexpression is associated with high cell proliferation and reduced disease-free survival in primary gastrointestinal diffuse large B-cell lymphoma.
abstract: OBJECTIVE
  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.
authors.affiliation: a Department of Hematology , Zhongnan Hospital of Wuhan University , 169 Dong Hu Road, Wuhan 430071 , China.
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.affiliation: a Department of Hematology , Zhongnan Hospital of Wuhan University , 169 Dong Hu Road, Wuhan 430071 , China.
authors.forename: Shangqin
authors.initials: S
authors.lastname: Liu
authors.affiliation: a Department of Hematology , Zhongnan Hospital of Wuhan University , 169 Dong Hu Road, Wuhan 430071 , China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: a Department of Hematology , Zhongnan Hospital of Wuhan University , 169 Dong Hu Road, Wuhan 430071 , China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.affiliation: a Department of Hematology , Zhongnan Hospital of Wuhan University , 169 Dong Hu Road, Wuhan 430071 , China.
authors.forename: Xuelan
authors.initials: X
authors.lastname: Zuo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000502:physiology; D018572:Disease-Free Survival; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D064246:Mad2 Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged
chemical_list: D019394:Ki-67 Antigen; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins
keywords: B-cell lymphoma-6 gene (BCL-6); Mitotic arrest deficiency protein 2 (Mad2); Nuclear associated antigen (Ki-67); Primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL)