title: Association between Hepatitis C Virus Infection, p53 Phenotypes, and Gene Variants of Adenomatous Polyposis Coli in Hepatocellular Carcinomas.
abstract: OBJECTIVE
  To investigate the clinical value of p53 codon 72 single nucleotide polymorphisms (SNPs) and variants of adenomatous polyposis coli (APC) in hepatocellular carcinomas (HCCs).
  
  
  METHODS
  DNA and RNA from 51 HCCs and their matching, uninvolved liver tissues were analyzed for p53 mutations, and the methylation and expression of APC variants were determined. Proliferation of each HCC was assessed by Ki67 immunohistochemistry. The results were correlated with the demographic and clinicopathologic features and patient survival.
  
  
  RESULTS
  Of 51 HCCs, 12% exhibited missense p53 mutations. SNP analysis of p53 codon 72 demonstrated the highest prevalence of the Arg/Arg (56%) phenotype, followed by Arg/Pro (33%) and Pro/Pro (11%). Four of five cases with the Pro/Pro phenotype were African Americans (AAs). All five cases with the Pro/Pro phenotype had hepatitis C virus (HCV) infections, a high Ki67 index, and lower median survival (15.5 months) compared to those with Arg/Arg or Arg/Pro phenotypes (32 months). The overall frequency of APC methylation was 31%, which was found predominantly in Caucasians. There was lower mRNA expression of APC variants-2 and -3 in both HCCs and corresponding adjacent, uninvolved liver tissues as compared to APC variant-1. The expression of APC variant-3, but not variants-1 and -2, was lower in HCCs relative to uninvolved tissues. Expression of all APC variants was lower in HCCs with APC methylation relative to HCCs without APC methylation, and low expression of APC variant-2 was associated with the Pro/Pro phenotype.
  
  
  CONCLUSIONS
  These findings suggest that, for AA patients with HCCs, the p53 Pro/Pro phenotype and low expression of APC variant-2 are associated with aggressive tumor behavior, HCV infection, and poor clinical outcome.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, USA.
authors.forename: Leona N
authors.initials: LN
authors.lastname: Council
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, USA; Department of Surgery, University of Alabama at Birmingham, USA.
authors.forename: Chandrakumar
authors.initials: C
authors.lastname: Shanmugam
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, USA; Comprehensive Cancer Center, University of Alabama at Birmingham, USA.
authors.forename: Esther A
authors.initials: EA
authors.lastname: Suswam
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, USA.
authors.forename: Venkat R
authors.initials: VR
authors.lastname: Katkoori
authors.affiliation: Comprehensive Cancer Center, University of Alabama at Birmingham, USA.
authors.forename: Martine J
authors.initials: MJ
authors.lastname: Heslin
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Hanna
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, USA.
authors.forename: Nirag C
authors.initials: NC
authors.lastname: Jhala
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, USA; Comprehensive Cancer Center, University of Alabama at Birmingham, USA.
authors.forename: Sooryanarayana
authors.initials: S
authors.lastname: Varambally
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, USA; Comprehensive Cancer Center, University of Alabama at Birmingham, USA.
authors.forename: Upender
authors.initials: U
authors.lastname: Manne
keywords: APC; HCV; Hepatocellular carcinoma; Survival; p53 codon 72 polymorphism