Prognostic significance of p53, mTOR, c-Met, IGF-1R, and HSP70 overexpression after the resection of hepatocellular carcinoma

Gut Liver. 2014 Jan;8(1):79-87. doi: 10.5009/gnl.2014.8.1.79. Epub 2014 Jan 13.

Abstract

Background/aims: The current study examines the expression of molecular biomarkers in hepatocellular carcinoma (HCC) and whether these findings correlate with the clinicopathologic features of the disease and patient survival.

Methods: We analyzed the immunohistochemical expression of p53, mammalian target of rapamycin (mTOR), c-Met, and insulin-like growth factor 1 receptor (IGF-1R) heat shock protein 70 (HSP70) with the clinicopathologic features of 83 HCCs.

Results: p53 expression was higher in the male patients with undifferentiated histological tumor grades, cirrhosis, and portal vein invasion. High 48 c-Met expression correlated with cirrhosis, and high mTOR expression correlated with the tumor grade and cirrhosis. High IGF-1R expression correlated with the tumor grade and cirrhosis. A multivariate analysis identified a significant relationship between the high expression of p53, tumor grade, and portal vein invasion. In addition, a high expression of mTOR was related to tumor grade and cirrhosis, and a high expression of HSP70 was related to portal vein invasion in a multivariate analysis. The Kaplan-Meier survival curve for patients with high versus low Edmondson grades and p53 expression was statistically significant.

Conclusions: p53, mTOR, and IGF-1R expression correlated with the Edmondson tumor grade in a univariate analysis, while p53 and mTOR correlated with the Edmondson tumor grade in a multivariate analysis. In addition, the tumor grade was found to predict survival. p53 was primarily related to the clinicopathologic features compared to other markers, and it is a poor prognostic factor of survival.

Keywords: Carcinoma, hepatocellular; Receptor, IGF type 1; c-Met; mTOR; p53.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / surgery
  • Disease-Free Survival
  • Female
  • HSP70 Heat-Shock Proteins / metabolism
  • Humans
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins c-met / metabolism
  • Receptor, IGF Type 1 / metabolism
  • Retrospective Studies
  • Risk Factors
  • TOR Serine-Threonine Kinases / metabolism
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Biomarkers, Tumor
  • HSP70 Heat-Shock Proteins
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins c-met
  • Receptor, IGF Type 1
  • TOR Serine-Threonine Kinases