Nuclear Expression of Hepatitis B Virus X Protein Is Associated with Recurrence of Early-Stage Hepatocellular Carcinomas: Role of Viral Protein in Tumor Recurrence.
- Author:
Jing JIN
1
;
Hae Yoen JUNG
;
Kyu Ho LEE
;
Nam Joon YI
;
Kyung Suk SUH
;
Ja June JANG
;
Kyoung Bun LEE
Author Information
- Publication Type:Original Article
- Keywords: Hepatitis B X protein; Hepatitis B surface antigens; Hepatitis B core antigens; Carcinoma, hepatocellular
- MeSH: alpha-Fetoproteins; Antigens, Surface; Carcinogenesis; Carcinoma, Hepatocellular*; Cytoplasm; Disease-Free Survival; Hepatitis B Core Antigens; Hepatitis B Surface Antigens; Hepatitis B virus*; Hepatitis B*; Hepatitis*; Hepatocytes; Humans; Immunohistochemistry; Recurrence*
- From:Journal of Pathology and Translational Medicine 2016;50(3):181-189
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND: Hepatitis B virus (HBV) plays well-known roles in tumorigenesis of hepatocellular carcinoma (HCC) in infected patients. However, HBV-associated protein status in tumor tissues and the relevance to tumor behavior has not been reported. Our study aimed to examine the expression of HBV-associated proteins in HCC and adjacent nontumorous tissue and their clinicopathologic implication in HCC patients. METHODS: HBV surface antigen (HBsAg), HBV core antigen (HBcAg), and HBV X protein (HBx) were assessed in 328 HBV-associated HCCs and in 155 matched nontumorous tissues by immunohistochemistry staining. RESULTS: The positive rates of HBsAg and cytoplasmic HBx staining in tumor tissue were lower than those in nontumorous tissue (7.3% vs. 57.4%, p < .001; 43.4% vs. 81.3%, p < .001). Conversely, nuclear HBx was detected more frequently in tumors than in nontumorous tissue (52.1% vs. 30.3%, p < .001). HCCs expressing HBsAg, HBcAg, or cytoplasmic HBx had smaller size; lower Edmondson-Steiner (ES) nuclear grade, pT stage, and serum alpha-fetoprotein, and less angioinvasion than HCCs not expressing HBV-associated proteins. Exceptionally, nuclear HBx-positive HCCs showed higher ES nuclear grade and more frequent large-vessel invasion than did nuclear HBx-negative HCCs. In survival analysis, only nuclear HBx-positive HCCs had shorter disease-free survival than nuclear HBx-negative HCCs in pT1 and ES nuclear grade 1-2 HCC subgroup (median, 126 months vs. 35 months; p = .015). CONCLUSIONS: Our data confirmed that expression of normal HBV-associated proteins generally decreases in tumor cells in comparison to nontumorous hepatocytes, with the exception of nuclear HBx, which suggests that nuclear HBx plays a role in recurrence of well-differentiated and early-stage HCCs.
