Clinicopathological correlates of aspartyl(asparaginyl)β-hydroxylase over-expression in cholangiocarcinoma
Clinicopathological correlates of aspartyl(asparaginyl)β-hydroxylase over-expression in cholangiocarcinoma
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DOI：
10.1016/j.cdp.2004.06.001
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发表时间：
2004-01-01
影响因子：
--
通讯作者：
de la Monte, SM
中科院分区：
文献类型：
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作者：
Maeda, T;Taguchi, K;de la Monte, SM
门冬酰胺基β-羟化酶（AAH）在手术切除的肝内胆管癌中的表达与肿瘤大小显著相关。生长类型、分化程度、血管侵犯和术后预后。AAH可能在调节人肝内胆管癌的侵袭性或转移性肿瘤细胞生长中起作用。背景：最近的研究表明，AAH基因在大多数胆管癌中表达增加。本研究旨在探讨AAH的高表达或低表达与肝内胆管细胞癌（ICC）临床病程的关系。研究方法：检测了50例手术切除的原发性ICC、12例正常肝脏和12例原发性硬化性胆管炎（PSC）中AAH的表达。用抗人AAH蛋白的FB-50单克隆抗体对切片进行免疫组化染色。根据代码检查切片，并对AAH免疫反应性的相对水平进行分级。分析了多个临床和组织病理学变量的结果，以确定ICC中AAH表达的相关性。结果：50例ICC中46例（92%）呈AAH免疫反应。而12例正常肝和12例PSC标本AAH均为阴性。在ICC标本中，AAH免疫反应性的最高水平被检测到的浸润边缘，接口与未涉及的肝组织，和最低水平发生在肿瘤的中心部分。多因素分析显示AAH高表达与肿瘤大小（P <0.05）、浸润性生长方式（P <0.01）、组织学分级（P <0.01）、血管侵犯（P <0.05）和预后不良（P <0.05）有关。结论：这些发现表明，AAH在调节人ICC的侵袭性或转移性肿瘤细胞生长中具有重要作用，并且高水平的AAH表达与不良预后相关。(C)2004年国际预防肿瘤学会。由爱思唯尔有限公司出版。保留所有权利。
Aspartyl (asparaginyl) beta-hydroxylase (AAH) expression in surgically resected intrahepatic cholangiocarcinoma significantly correlated with tumor size. growth type, differentiation, vascular invasion, and prognosis after surgery. AAH may have a role in regulating invasive or metastatic tumor cell growth of human intrahepatic cholangiocarcinoma. Background: Recent studies demonstrated increased expression of the AAH gene in the majority of cholangiocarcinomas. The present study was undertaken to determine the relationship between high or low levels of AAH expression and the clinical course of intrahepatic cholangiocarcinoma (ICC). Methods: AAH expression was examined in 50 surgically resected primary ICCs, 12 samples of normal liver, and 12 cases of primary sclerosing cholangitis (PSC). The sections were evaluated by immunohistochemical staining with the FB-50 monoclonal antibody to human AAH protein. The sections were examined under code and graded for relative levels of AAH immunoreactivity. The results were analyzed with respect to multiple clinical and histopathological variables to determine correlates of AAH expression in ICCs. Results: Forty-six of the 50 (92%) ICCs had AAH immunoreactivity. whereas the 12 normal liver and 12 PSC specimens were AAH negative. In the ICC specimens, the highest levels of AAH immunoreactivity were detected at the infiltrating margins that interfaced with uninvolved liver tissue, and the lowest levels occurred in the central portions of the tumors. Multivariate analysis demonstrated that high levels of AAH expression were correlated with tumor size (P < 0.05), infiltrative growth pattern (P < 0.01), aggressive histological grade (P < 0.01), vascular invasion (P < 0.05), and poor prognosis (P < 0.05). Conclusions: These findings suggest that AAH has an important role in regulating invasive or metastatic tumor cell growth of human ICC, and that high levels of AAH expression correlate with poor prognosis. (C) 2004 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved.