title: Overexpression of α-methylacyl-CoA racemase is associated with CTNNB1 mutations in hepatocellular carcinomas.
abstract: OBJECTIVE
  α-Methylacyl-CoA racemase (AMACR) is expressed in the majority of hepatocellular carcinomas (HCCs) at variable levels, but the significance of AMACR overexpression remains elusive. The aim of this study was to investigate the relationship between AMACR expression and the presence of CTNNB1 mutations in HCCs.
  
  
  RESULTS
  The expression of AMACR and GLUL, an established downstream target of β-catenin was examined in HCCs, by quantitative reverse transcription polymerase chain reaction (PCR), and the expression of their protein products by immunohistochemistry. The quantitative reverse transcription PCR analysis showed that the expression of AMACR was significantly higher in HCCs with CTNNB1 mutations than in mutation-negative HCCs or normal livers, like the expression of GLUL. Immunohistochemistry also showed that strong AMACR protein expression was closely correlated with the presence of CTNNB1 mutations. HCCs with CTNNB1 mutations and those with AMACR overexpression frequently exhibited bile production.
  
  
  CONCLUSIONS
  The overexpression of AMACR was closely correlated with the presence of CTNNB1 mutations in HCCs. AMACR is a putative target of β-catenin as well as an excellent immunohistochemically detectable marker of HCCs with CTNNB1 mutations. As AMACR is physiologically involved in bile acid synthesis, the current observation implies a regulatory role of β-catenin in bile acid metabolism.
authors: Pathology Division, National Cancer Centre Research Institute, Tokyo, Japan.
authors: Shigeki
authors: S
authors: Sekine
authors: Reiko
authors: R
authors: Ogawa
authors: Hidenori
authors: H
authors: Ojima
authors: Yae
authors: Y
authors: Kanai
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019998:Racemases and Epimerases / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; D051176:beta Catenin; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase