肝细胞再生结节、变异肝细胞结节与肝细胞癌之间的对照观察

A comparative observation on regenerative nodules, altered hepatocyte nodules and hepatocellularcarcinomas

目的研究变异肝细胞结节（NAH）的形成和进展及其与肝细胞癌（HCC）的关系。方法对HCC、来自癌周肝组织的NAH和普通再生结节（ORN）各50个进行组织学观察；通过免疫组织化学反应显示不同病变中乙型肝炎病毒（HBV）抗原表达水平，评价细胞增殖活性，检测p53蛋白异常积累。结果在50例HCC切除标本的癌周肝组织中均检测到多个变异肝细胞病灶（FAH）和NAH，自FAH到HCC的演进过程中存在一系列连续的结构和形态变化；与ORN相比，NAH和HCC中HBV表面及核心抗原的表达水平逐渐降低『阳性率分别为70％（35／50）、50％（25／50）、10％（5／50）和60％（30／50）、40％（20／50）、6％（3／50）I（P〈0．05），Ki一67抗原标记指数逐渐升高[分别为（0．58±0．49）％、（2．46±1．05）％和（40．36±26．27）％]（P〈0．05），而p53蛋白异常积聚仅见于部分HCC[46％（23／50）1，其程度随组织学分级的升高而增高[Ⅰ级、Ⅱ级和Ⅲ级病变中分别为13％（1／8）、41％（11／27）和73％（11／15）].结论NAH在慢性乙型肝炎和肝硬变的切除标本中也可以检测到，有一系列的形态学改变可供识别，具有较高的增殖活性：NAH代表一种常见的HCC前期病变，可用于HCC发生的监测。

Objective To describe the development of nodules of altered hepatocytes （NAH） in chronic hepatitis B and to reveal progression of the nodules to hepatocellular carcinoma （HCC）. Methods HCC, NAH amt ordinary regenerative nodules （URN） were identified and compared histologically. Expression levels of hepatitis B virus （HBV） antigens, mitoaetivity and p53 accumulation in these lesions were evaluated by immunohistochemistry. Results Multiple loci of altered hepatocytes （FAH） and NAH were identified in the liver parenehyma surrounding HCC in all of the samples examined. Sequential architectural and cellular changes were observed during the progression of FAH to NAH and HCC. Expression levels of HBV surface and cure antigens were found to be significantly decreased in URN, NAH and HCC, with their positive rates being 70 % （35/50）, 50 % （25/50）, 10 % （5/50） and 60 % （30/50）, 40 % （20/50）, 6 % （3/50）, respectively （P 〈0.05）. Ki-67-1abelling indices were determined to be （0.58-＋0.49） %, （2.46±1.05） % and （40.36±26.27） % in these lesions, respectively （P 〈0.05）. Nuclear p53 accumulation was found only in HCC. Its occurrence was associated to a high histological grade, with its frequencies being 13 % （1/8）, 41% （11/27） and 73 % （11/15） in grade 1, 2 and 3 lesions, respectively. Conclusion NAH lesions, identified by their morphologic features and mitoaetivity elevation, are detectable in resected liver samples with chronic hepatitis B and cirrhosis. They represent a common HCC precursor and can be used as a surrogate marker for the surveillance of high-risk individuals.