title: AKR1B10 expression is associated with less aggressive hepatocellular carcinoma: a clinicopathological study of 168 cases.
abstract: OBJECTIVE
  The detoxification enzyme AKR1B10, a member of the aldo-keto reductase superfamily, is discussed as a new biomarker candidate for hepatocellular carcinoma (HCC). Only rare clinicopathological data on AKRB1B10 in HCC exist. This retrospective study determines the diagnostic and prognostic relevance of AKR1B10 expression in HCC and its relationship to a series of clinicopathological parameters including underlying aetiological factors.
  
  
  METHODS
  A series of 168 patients with HCCs treated either by surgical resection (n=92) or liver transplantation (n=76) were investigated after construction of a tissue micro-array. Immunohistochemically confirmed AKR1B10 expression was correlated with clinicopathologically relevant parameters as well as proliferative activity (indicated by Ki-67 immunostaining) and apoptosis (terminal deoxyribonucleotide transferase-mediated dUTP nick-end labelling).
  
  
  RESULTS
  AKR1B10 overexpression is significantly associated with lower pT-classification (P=0.030) and highly statistically associated with an underlying viral hepatitis (P<0.001) and the presence of cirrhosis (P<0.001). In addition, loss of AKR1B10 expression correlates with increased proliferative activity (Ki-67, P=0.001). Kaplan-Meier survival analysis of the resection group reveals a poorer prognosis in patients with AKR1B10-negative HCCs compared with patients with strongly positive HCCs (P=0.046).
  
  
  CONCLUSIONS
  This study confirms and expands data on the expression of AKR1B10 in HCC, suggesting that this enzyme is a valuable novel biomarker candidate for staging of HCC, especially in patients with underlying virus hepatitis or cirrhosis, and may present a new therapeutic target for multimodal therapy concepts. We confirm its prognostic value and conclude that high expression of AKR1B10 reflects a less aggressive tumour behaviour.
authors.affiliation: Institute of Pathology and Neuropathology, Essen University Hospital, University of Duisburg-Essen, Essen, Germany.
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Schmitz
authors.forename: Georgios C
authors.initials: GC
authors.lastname: Sotiropoulos
authors.forename: Hideo A
authors.initials: HA
authors.lastname: Baba
authors.forename: Kurt W
authors.initials: KW
authors.lastname: Schmid
authors.forename: Doris
authors.initials: D
authors.lastname: Müller
authors.forename: Andreas
authors.initials: A
authors.lastname: Paul
authors.forename: Thomas
authors.initials: T
authors.lastname: Auer
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gamerith
authors.forename: Judith
authors.initials: J
authors.lastname: Loeffler-Ragg
mesh_terms: D000449:Aldehyde Reductase / Q000032:analysis*; D000074408:Aldo-Keto Reductases; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D017115:Catheter Ablation; D049109:Cell Proliferation; D016461:Chemoembolization, Therapeutic; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005260:Female; D006498:Hepatectomy; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase