Overexpression of α-methylacyl-CoA racemase is associated with CTNNB1 mutations in hepatocellular carcinomas

Shigeki Sekine, Reiko Ogawa, Hidenori Ojima, Yae Kanai

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Aims: 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. Methods and 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.

Original languageEnglish
Pages (from-to)712-719
Number of pages8
JournalHistopathology
Volume58
Issue number5
DOIs
Publication statusPublished - 2011 Apr
Externally publishedYes

Fingerprint

Racemases and Epimerases
Coenzyme A
Hepatocellular Carcinoma
Mutation
Catenins
Bile Acids and Salts
Reverse Transcription
Immunohistochemistry
Polymerase Chain Reaction
Bile
Proteins
Observation

Keywords

  • β-catenin
  • AMACR
  • Hepatocellular carcinoma

ASJC Scopus subject areas

  • Histology
  • Pathology and Forensic Medicine

Cite this

Overexpression of α-methylacyl-CoA racemase is associated with CTNNB1 mutations in hepatocellular carcinomas. / Sekine, Shigeki; Ogawa, Reiko; Ojima, Hidenori; Kanai, Yae.

In: Histopathology, Vol. 58, No. 5, 04.2011, p. 712-719.

Research output: Contribution to journalArticle

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