Elevated expression of valosin-containing protein (p97) in hepatocellular carcinoma is correlated with increased incidence of tumor recurrence.

Abstract

PURPOSE:

Valosin-containing protein (VCP; also known as p97) has been shown to be associated with antiapoptotic function and metastasis via activation of the nuclear factor-kappaB signaling pathway. In this study, association of VCP expression with recurrence of hepatocellular carcinoma (HCC) and patient survival was examined.

PATIENTS AND METHODS:

VCP expression in 170 patients (139 male and 31 female) with ages ranging from 31 to 81 years (median, 61 years) was analyzed by quantitative reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry, in which staining intensity in tumor cells was categorized as weaker (level 1) or equal to or stronger (level 2) than that in endothelial cells.

RESULTS:

Immunohistochemically, 57 patients (35.2%) showed level 1, and 105 patients (64.8%) showed level 2, VCP expression. Quantitative RT-PCR analysis revealed higher VCP mRNA expression in level 2 patients (n = 7) than level 1 (n = 4) (P <.05). Patients with VCP-level 2 HCC showed higher rate of portal vein invasion in the tumor (P <.01) and poorer disease-free and overall survival (P <.0001 and P <.05, respectively) compared with level 1 patients. Multivariate analysis revealed VCP expression level, tumor multiplicity, and degree of fibrosis in the noncancerous liver tissue to be independent prognosticators for disease-free and overall survival. VCP level was an indicator for disease-free survival in each early- (I and II) and advanced- (III and IV) stage group of pathologic tumor-node-metastasis classification (P <.001 and P <.01, respectively).

CONCLUSION:

VCP expression level has prognostic significance for disease-free and overall survival of patients with HCC.

• Authors: Shinji Yamamoto, Yasuhiko Tomita, Shoji Nakamori, Yoshihiko Hoshida, Hiroaki Nagano, Keizo Dono, Koji Umeshita, Masato Sakon, Morito Monden, Katsuyuki Aozasa
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 21 Issue 3 Pg. 447-52 (Feb 01 2003) ISSN: 0732-183X [Print] United States
• PMID: 12560433 (Publication Type: Journal Article)

Chemical References

• Cell Cycle Proteins
• Adenosine Triphosphatases
• VCP protein, human
• Valosin Containing Protein

Topics

• Adenosine Triphosphatases
• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Hepatocellular (genetics, pathology, surgery)
• Cell Cycle Proteins (biosynthesis)
• Disease-Free Survival
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Liver Cirrhosis
• Liver Neoplasms (genetics, pathology, surgery)
• Male
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Neoplasm Recurrence, Local
• Predictive Value of Tests
• Prognosis
• Reverse Transcriptase Polymerase Chain Reaction
• Valosin Containing Protein