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

 【摘要】 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 在本组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；在ORN到NAH和HCC的演进过程中HBV表面及核心抗原的表达水平逐渐降低，Ki-67抗原表及指数逐渐升高，而p53蛋白异常积聚仅见于HCC，其程度随组织学分级的升高而增高。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可能代表一种常见的HCC前期病变而用于HCC发生的监测。

A comparative observation on regenerative nodules, altered hepatocyte nodules and hepatocellular carcinomas

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 and ordinary regenerative nodules (ORN) were identified and compared histologically. Expression levels of hepatitis B virus (HBV) antigens, mitoactivity and p53 accumulation in these lesions were evaluated by immunohistochemistry. Results Multiple foci of altered hepatocytes (FAH) and NAH were identified in the liver parenchyma 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 core antigens were found to be significantly decreased in ORN, 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 mitoactivity 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.