Avellini C, Orsaria M, Baccarani U, Adani G L, Lorenzin D, Bresadola V, Bresadola F, Beltrami C A
Department of Pathology, University Hospital Udine, Udine, Italy.
Transplant Proc. 2010 May;42(4):1204-8. doi: 10.1016/j.transproceed.2010.03.045.
Apurinic apyrimidinic endonuclease (APE1)/redox effector factor 1 (Ref-1), which is a multifunction protein involved in both transcriptional regulation of gene expression during adaptive cellular responses to oxidative stress and in the base excision repair pathway of DNA lesions generated as a consequence of oxidant-induced base damage, contributes to the maintenance of genome stability. APE1/Ref-1 is normally localized in the nucleus; cytoplasmic localization observed in several tumors has been correlated with a poor prognosis. Hepatocellular carcinoma (HCC) grading is an essential tool to predict the risk of relapse and patient prognosis, particularly in patients undergoing liver transplantation (OLT). The aim of this study was to identify the role of APE1/Ref-1 in predicting a posttransplant HCC relapse. We studied 48 patients transplanted for HCC to define grading as well as nuclear and cytoplasmic APE1/Ref-1 expression within neoplastic versus nonneoplastic parenchyma. We defined a cutoff of 60% of cytoplasmic APE1/Ref-1 expression to identify positive cases. At a minimum of 1.5-year follow-up after transplantation, 32 patients are alive and 16 patients are deceased after HCC relapse. Among low-grade HCC (grades 1 and 2), 76% of cases are alive; only 34% showed cytoplasmic APE1/Ref-1 immunoreactivity. Among the high-grade cases (grades 3 and 4), 50% were alive with 64% showing cytoplasmic immunoreactivity. Nuclear reactivity was generally similar either in neoplastic or in cirrhotic livers, irrespective of the grade. These data seemed to support the hypothesis of a predictive role of APE1/Ref-1 for HCC risk of relapse, which together with tumor grade by analysis of a pretransplant needle biopsy should aid decision making for OLT.
脱嘌呤嘧啶内切酶（APE1）/氧化还原效应因子1（Ref-1）是一种多功能蛋白，参与细胞对氧化应激的适应性反应过程中基因表达的转录调控，以及由氧化剂诱导的碱基损伤所产生的DNA损伤的碱基切除修复途径，有助于维持基因组稳定性。APE1/Ref-1通常定位于细胞核；在几种肿瘤中观察到的细胞质定位与预后不良相关。肝细胞癌（HCC）分级是预测复发风险和患者预后的重要工具，尤其是在接受肝移植（OLT）的患者中。本研究的目的是确定APE1/Ref-1在预测移植后HCC复发中的作用。我们研究了48例因HCC接受移植的患者，以确定肿瘤组织与非肿瘤组织中的分级以及细胞核和细胞质中APE1/Ref-1的表达。我们将细胞质中APE1/Ref-1表达60%作为临界值来确定阳性病例。移植后至少随访1.5年，32例患者存活，16例患者在HCC复发后死亡。在低级别HCC（1级和2级）中，76%的病例存活；只有34%显示细胞质APE1/Ref-1免疫反应性。在高级别病例（3级和4级）中，50%存活，64%显示细胞质免疫反应性。无论分级如何，肿瘤组织或肝硬化肝脏中的细胞核反应性通常相似。这些数据似乎支持了APE1/Ref-1对HCC复发风险具有预测作用的假设，通过分析移植前穿刺活检获得的该指标与肿瘤分级一起应有助于OLT的决策制定。
