title: Metastatic tumor antigen 1 is closely associated with frequent postoperative recurrence and poor survival in patients with hepatocellular carcinoma.
abstract: Metastatic tumor antigen 1 (MTA1) is known to play a role in angiogenic processes as a stabilizer of hypoxia-inducible factor 1-alpha (HIF1-alpha). In this study, we examined whether overexpression of MTA1 affects the recurrence of hepatocellular carcinoma (HCC) after surgical resection and the survival of the patients. A total of 506 HCC patients who underwent hepatic resection were included in the study. They were followed up for a median of 43 months (range, 1-96 months) after hepatectomy. MTA1 expression levels were determined by the proportion of immunopositive cells (none, all negative; +, <50%; ++, >50%). The relationships between MTA1 expression and the HCC histological features, the appearance of recurrent HCC after surgical resection, and the survival of the patients were examined. Eighty-eight cases (17%) of the HCCs were positive for MTA1, although the surrounding liver tissues were all negative for MTA1; 62 cases were + and 26 cases were ++. Increased MTA1 expression levels in HCC were correlated with larger tumors (P = 0.04), perinodal extension (P = 0.03), and microvascular invasion (P = 0.008). Histological differentiation had marginal significance (P = 0.056). However, there was no association between MTA1 expression and age, sex, Child-Pugh class, and capsule invasion of HCC. Interestingly, MTA1 expression levels were significantly greater in hepatitis B virus (HBV)-associated HCC compared with hepatitis C virus (HCV)-associated HCC (P = 0.017). The cumulative recurrence rates of MTA1-positive HCCs were markedly greater than those of MTA1-negative HCCs (P < 0.0001). The cumulative survival rates of patients with MTA1-positive HCCs were significantly shorter than those of patients with MTA1-negative HCCs (P < 0.0001). In conclusion, our data indicate that MTA1 is closely associated with microvascular invasion, frequent postoperative recurrence, and poor survival of HCC patients, especially in those with HBV-associated HCC.
authors.affiliation: Department of Internal Medicine, University of Inje College of Medicine, Seoul, Korea.
authors.forename: Soo Hyung
authors.initials: SH
authors.lastname: Ryu
authors.forename: Young-Hwa
authors.initials: YH
authors.lastname: Chung
authors.forename: Hyunseung
authors.initials: H
authors.lastname: Lee
authors.forename: Jeong A
authors.initials: JA
authors.lastname: Kim
authors.forename: Hyun Deok
authors.initials: HD
authors.lastname: Shin
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Min
authors.forename: Dong Dae
authors.initials: DD
authors.lastname: Seo
authors.forename: Myoung Kuk
authors.initials: MK
authors.lastname: Jang
authors.forename: Eunsil
authors.initials: E
authors.lastname: Yu
authors.forename: Kyu-Won
authors.initials: KW
authors.lastname: Kim
mesh_terms: D000368:Aged; D002196:Capillaries / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000401:mortality* / Q000601:surgery; D004617:Embolism / Q000175:diagnosis; D005260:Female; D006655:Histone Deacetylases / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000401:mortality* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D011184:Postoperative Period; D011379:Prognosis; D012097:Repressor Proteins / Q000032:analysis* / Q000378:metabolism; D015534:Trans-Activators; D016896:Treatment Outcome
chemical_list: C089320:MTA1 protein, human; D012097:Repressor Proteins; D015534:Trans-Activators; D006655:Histone Deacetylases