Clinicopathologic significance of mitotic arrest defective protein 2 overexpression in hepatocellular carcinoma.
Mitotic arrest defective protein 2 (MAD2) gene plays a central role in the mitotic checkpoint. Elevated MAD2 expression was observed in a number of human malignancies; its role in the development of hepatocellular carcinoma is still not understood and is controversial. The purpose of this study was to investigate the clinicopathologic significance of MAD2 expression in hepatocellular carcinoma. The MAD2 protein and its messenger RNA levels were measured in hepatocellular carcinomas, high-grade dysplastic nodules, and their paired nontumorous liver tissues by quantitative real-time polymerase chain reaction, Western blot, and immunohistochemistry. The results showed that MAD2 at both messenger RNA and protein levels was overexpressed in 8 of 9 high-grade dysplastic nodules and in 51 of 58 hepatocellular carcinomas, including 12 of 14 unifocal small hepatocellular carcinomas. There was a tendency for MAD2 expression to increase in the process of this multistep carcinogenesis. A significantly high tumor MAD2 immunostaining was associated with the progression of histologic grade and the overall low survival. In conclusion, MAD2 is overexpressed frequently in hepatocellular carcinoma, including high-grade dysplastic nodules and early-stage small hepatocellular carcinoma, indicating that overexpression of MAD2 plays a role in the development and progression of hepatocellular carcinoma. It may be an early event in hepatocarcinogenesis and could be used as a potential prognostic indicator.
Zhang
Shu-Hui
SH
Department of Pathology, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437 China. zhangshuhui100@sohu.com
Xu
Ai-Min
AM
Chen
Xin-Fang
XF
Li
Di-Hua
DH
Sun
Man-Ping
MP
Wang
Yu-Jia
YJ
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D064246:Mad2 Proteins; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D012097:Repressor Proteins / Q000378:metabolism*; D015996:Survival Rate; D046888:Tissue Array Analysis; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D012097:Repressor Proteins