Institute of Pathology and Neuropathology, Essen University Hospital, University of Duisburg-Essen, Essen, Germany.
Liver Int. 2011 Jul;31(6):810-6. doi: 10.1111/j.1478-3231.2011.02511.x. Epub 2011 Mar 29.
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.
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).
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).
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.
背景/目的：解毒酶 AKR1B10 是醛酮还原酶超家族的成员，被认为是肝细胞癌（HCC）的新生物标志物候选物。关于 HCC 中 AKRB1B10 的临床病理数据很少。本回顾性研究确定了 HCC 中 AKR1B10 表达的诊断和预后相关性及其与一系列临床病理参数（包括潜在病因因素）的关系。
通过构建组织微阵列，对 168 例接受手术切除（n=92）或肝移植（n=76）治疗的 HCC 患者进行了研究。免疫组织化学证实 AKR1B10 表达与临床病理相关参数以及增殖活性（通过 Ki-67 免疫染色表示）和凋亡（末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记）相关。
AKR1B10 过表达与较低的 pT 分类显著相关（P=0.030），与潜在的病毒性肝炎（P<0.001）和肝硬化（P<0.001）高度相关。此外，AKR1B10 表达缺失与增殖活性增加相关（Ki-67，P=0.001）。切除组的 Kaplan-Meier 生存分析显示，AKR1B10 阴性 HCC 患者的预后较 AKR1B10 强阳性 HCC 患者差（P=0.046）。
本研究证实并扩展了 AKR1B10 在 HCC 中的表达数据，表明该酶是 HCC 分期的有价值的新型生物标志物候选物，特别是在有潜在病毒肝炎或肝硬化的患者中，并且可能成为多模式治疗概念的新治疗靶点。我们确认了其预后价值，并得出结论，AKR1B10 的高表达反映了肿瘤行为的侵袭性较小。
