Premium
AKR1B10 expression is associated with less aggressive hepatocellular carcinoma: a clinicopathological study of 168 cases
Author(s) -
Schmitz Klaus J.,
Sotiropoulos Georgios C.,
Baba Hideo A.,
Schmid Kurt W.,
Müller Doris,
Paul Andreas,
Auer Thomas,
Gamerith Gabriele,
LoefflerRagg Judith
Publication year - 2011
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2011.02511.x
Subject(s) - hccs , hepatocellular carcinoma , medicine , cirrhosis , immunostaining , biomarker , immunohistochemistry , liver transplantation , cancer , pathology , transplantation , cancer research , gastroenterology , biology , biochemistry
Background/Aims: 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.