RRC ID 43644
Author Wu LC, Chen LT, Tsai YJ, Lin CM, Lin CY, Tian YF, Sheu MJ, Uen YH, Shiue YL, Wang YH, Yang SJ, Wu WR, Li SH, Iwamuro M, Kobayasshi N, Huang HY, Li CF.
Title Alpha-methylacyl coenzyme A racemase overexpression in gallbladder carcinoma confers an independent prognostic indicator.
Journal J Clin Pathol
Abstract AIMS:Increased β-oxidation of branched-chain fatty acids provides an additional metabolic advantage for cancer cells thereby enhancing tumour development and progression. Alpha-methylacyl coenzyme A racemase (AMACR) is an enzyme essential for the catabolism of branched-chain fatty acids that allows their subsequent β-oxidation and thus plays an important role in generating biological energy. However, the expression of AMACR has never been systemically investigated in gallbladder carcinoma. This study evaluated the expression status, associations with clinicopathological variables and prognostic implications of AMACR in a well-defined cohort of gallbladder carcinoma and confirmed their expression status in gallbladder carcinoma cells.
METHODS:AMACR immunostaining was assessable in 89 cases on tissue microarrays of gallbladder carcinoma, and it was correlated with clinicopathological factors and patient survival. In three gallbladder carcinoma cell lines and one non-tumorigenic cholangiocyte, AMACR mRNA expression was measured by real-time reverse transcription PCR and the endogenous expression of AMACR protein was analysed by western blotting.
RESULTS:AMACR overexpression was significantly associated with an advanced primary tumour status (p=0.027) and American Joint Committee on Cancer stage (p=0.027), an increased histological grade (p=0.002) and vascular invasion (p=0.017). Importantly, AMACR overexpression independently predicted worse disease-specific survival (p=0.0452, RR 1.887). Expression levels of AMACR mRNA and total protein in various cells were comparable. The abundance of AMACR expression increased in tumour cells and was even higher in the metastatic cell line.
CONCLUSIONS:In primary gallbladder carcinoma, AMACR overexpression was correlated with important prognosticators and independently portended worse outcomes, highlighting the potential prognostic and therapeutic utility of AMACR in gallbladder carcinoma.
Volume 65(4)
Pages 309-14
Published 2012-4-1
DOI 10.1136/jclinpath-2011-200489
PII jclinpath-2011-200489
PMID 22267983
MeSH Adult Aged Aged, 80 and over Biomarkers, Tumor / metabolism* Blotting, Western Female Gallbladder / enzymology* Gallbladder Neoplasms / enzymology* Gallbladder Neoplasms / mortality Humans Immunohistochemistry Kaplan-Meier Estimate Male Middle Aged Prognosis Racemases and Epimerases / metabolism* Real-Time Polymerase Chain Reaction Tumor Cells, Cultured
IF 2.46
Times Cited 14
WOS Category PATHOLOGY
Resource
Human and Animal Cells TGBC1TKB(RCB1129) TGBC2TKB(RCB1130)