Combined loss of expression of O6-methylguanine-DNA methyltransferase and hMLH1 accelerates progression of hepatocellular carcinoma.
OBJECTIVE
O(6)-methylguanine-DNA methyltransferase (MGMT) and human Mut L homologue 1 (hMLH1) are proteins that play an important role in DNA repair. No reports have yet described whether deficient MGMT and hMLH1 expression correlates with tumor progression and the prognosis of patients with hepatocellular carcinoma (HCC).


METHODS
Using immunohistochemical analysis, we evaluated the expression status of MGMT and hMLH1 protein in 60 paraffin-embedded samples from consecutive patients with curatively resected HCC.


RESULTS
The lack of expression of both MGMT and hMLH1 in HCCs (n = 7) correlated with advanced pTNM stage (P = 0.039), as compared with HCCs expressing both proteins (n = 25). The absence of both MGMT and hMLH1 was a significant indicator of malignant potential. The expression status of both MGMT and hMLH1 was a predictive factor for overall survival in patients with HCC (P < 0.001).


CONCLUSIONS
HCC lacking both MGMT and hMLH1 is correlated with an advanced stage and a poor prognosis. The expression status of both repair proteins is a predictive prognostic marker in patients with HCC after surgical resection.
Matsukura
Shiroh
S
Department of Surgery, Saga Medical School, Saga, Japan.
Miyazaki
Kohji
K
Yakushiji
Hiroyuki
H
Ogawa
Akiomi
A
Chen
Yongxin
Y
Sekiguchi
Mutsuo
M
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D002352:Carrier Proteins; D004260:DNA Repair; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009367:Neoplasm Staging; D009687:Nuclear Proteins; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000096:biosynthesis*; D011379:Prognosis
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000070957:MutL Protein Homolog 1