APE1在肝细胞癌组织芯片表达及临床病理意义.docVIP

APE1在肝细胞癌组织芯片表达及临床病理意义 　 作者：郑智华, 黄爱民, 刘景丰, 臧盛兵, 高凌云, 陈水平 【摘要】 目的 探讨脱嘌呤/脱嘧啶核酸内切酶1(APE1)基因在原发性肝细胞癌(HCC)的表达及其与临床病理变化的关系。 方法 应用免疫组织化学方法,检测包含HCC及转移灶、癌旁肝硬化组织、癌旁慢性肝炎组织和正常肝组织的组织芯片中APE1的表达情况,结合临床病理资料进行统计分析。 结果 APE1在癌旁肝硬化组织、癌旁慢性肝炎组织和正常肝组织以细胞核表达为主,在HCC和转移灶组织以细胞质细胞核联合表达为主(Plt;0.01)。细胞质与细胞核染色强度均与HCC分级和转移密切相关(Plt;0.01),细胞质染色强度还与肿瘤包膜有无浸润有关(Plt;0.01)。 结论 APE1蛋白表达与HCC恶性表型有关,APE1蛋白过表达及细胞质表达的出现可能成为HCC预后不良的指标之一。 【关键词】 癌,肝细胞; 内切核酸酶类; 芯片分析技术; 免疫组织化学; 预后 ABSTRACT: Objective To study the association of apurinc/apyrimidinic endonuclease1(APE1) expression with clinicopathologic parameters in hepatocelluar carcinoma(HCC). Methods APE1 protein was detected in seven tissue chips, which contains HCC, para-carcinoma tissues, para-carcinoma choronic hepatitis tissues and normal liver tissues by immunohistochemistry. Detailed analysis of APE1 expression with clinicopathologic parameters was performed. Results APE1 was mainly detected in nuclei of para-carcinoma tissues, para-carcinoma chronic hepatitis tissues and normal liver tissues. While APE1 expressed in both nucleus and cytoplasm only found in HCC and metastatic tumor(Plt;0.01). A statistic significantty correlation between the positive degree of APE1 expression in both nucleus and cytoplasm with histological grade of HCC and metastasis(Plt;0.01). Furthermore, the positive degree in cytoplasm was correlated with capsule invasion(Plt;0.01). Conclusion The expression of APE1 is associated with the malignant phenotype of HCC. Overexpression and cytoplasm localization of APE1 can be used as a poorly prognostic marker for HCC. KEY WORDS: carcinoma,hepatocelluar; endonucleases; microchip analytical procedures; immunohistochemistry; prognosis 肝细胞癌(hepatocellular carcinoma,HCC)是我国最常见的恶性肿瘤之一,其癌变是一个多步骤的渐进过程,与慢性肝脏损伤、肝炎和肝硬化有关。脱嘌呤/脱嘧啶核酸内切酶1(APE1)是一种多功能的碱基切除修复途径的关键酶,具有脱嘌呤/脱嘧啶位点(AP位点)核酸内切酶(APE)活性,修复烷化剂、氧自由基、电离辐射等因素产生的DNA损伤。AP位点是DNA最常见的损伤位点之一,具有细胞毒性和基因毒性,若不能修复,可阻碍DNA的复制,导致基因突变、染色体微卫星不稳定性或细胞凋亡,最终可导致肿瘤的发生。APE1又名氧化还原因子1(Ref-1),可调节许多转录因子的DNA结合活性,参与细胞增殖、分化和细胞