J Korean Med Sci.  2001 Aug;16(4):424-432. 10.3346/jkms.2001.16.4.424.

Expression of the G1-S Modulators in Hepatitis B Virus-Related Hepatocellular Carcinoma and Dysplastic Nodule: Association of Cyclin D1 and p53 Proteins with the Progression of Hepatocellular Carcinoma

• Choi YL
• Park SH
• Jang JJ
• Park CK

• KMID: 648300
• DOI: http://doi.org/10.3346/jkms.2001.16.4.424

Abstract

Deranged expression of cell cycle modulators has been reported to contribute to the development and progression of hepatocellular carcinoma (HCC). However, their expression patterns remain poorly understood in hepatitis B virus (HBV)-related HCC, which constitutes about 65-70% of HCC in Korea. The aims of this study were to evaluate the expressions of G1-S modulators in HBV-related HCCs and dysplastic nodules (DNs), and to correlate with the histopathologic features of HCCs. Immunohistochemical expressions of cyclin D1, cyclin E, p53, p27, p21, p16, Rb, and PCNA proteins were investigated in 80 HCCs and 22 DNs. Cyclin D1 overexpression showed positive relationships with advanced tumor stage, poor differentiation, larger tumor size, microvascular invasion, intrahepatic meta-stasis, no tumor capsule formation, infiltrative growth, aberrant p53 expression, and high PCNA labeling index (LI) of HCC (p<0.05). Aberrant p53 expression showed positive relationship with poor differentiation of HCC (p<0.01). Expression of cyclin D1 or p53 was not observed in DNs. The p27 LI and p16 LI were lower in HCCs with intrahepatic metastasis (p<0.05). Cyclin D1 overexpression and aberrant p53 expression could be associated with the progression of HBV-related HCC, and might have a less crucial role in the DN-HCC sequence. In addition, elevated expression of p27 and p16 proteins might have inhibitory action to the intrahepatic metastasis of HBV-related HCC.

Keyword

Carcinoma, Hepatocellular; Dysplastic Nodule; Hepatitis B Virus; Protein cyclin D1; Protein p53; Protein p27; Protein p16

MeSH Terms

Adult
Aged
Carcinoma, Hepatocellular/chemistry/etiology/*pathology
Cyclin D1/*analysis
Female
G1 Phase
Hepatitis B/*complications
Human
Immunohistochemistry
Liver Neoplasms/chemistry/etiology/*pathology
Male
Microfilament Proteins/analysis
Middle Age
Precancerous Conditions/*virology
Proliferating Cell Nuclear Antigen/analysis
Protein p16/analysis
Protein p53/*analysis
Retinoblastoma Protein/analysis
S Phase