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

J Clin Oncol. 2003 Feb 1;21(3):447-52. doi: 10.1200/JCO.2003.06.068.

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.

MeSH terms

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

Substances

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