Large cell change of hepatocytes in chronic viral hepatitis represents a senescent-related lesion
Large cell change of hepatocytes in chronic viral hepatitis represents a senescent-related lesion
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DOI：
10.1016/j.humpath.2009.06.009
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发表时间：
2009-12-01
期刊：
影响因子：
3.3
通讯作者：
Nakanuma, Yasuni
中科院分区：
文献类型：
--
作者：
Ikeda, Hiroko;Sasaki, Motoko;Nakanuma, Yasuni
大细胞变化涉及肝细胞聚集，伴深染和细胞增大，但核/质比未增加。本研究调查了慢性病毒性肝炎的大细胞变化是否反映了细胞衰老，因为这两种情况之间的形态学相似性。在26份冷冻和82份福尔马林固定的肝脏标本中检测了衰老标志物（如衰老相关β-半乳糖苷酶、衰老相关异染色质病灶和p21）以及细胞动力学标志物（如Ki-67）的表达。大细胞改变常见于组织学分期较晚的慢性B型肝炎，尤其是肝细胞癌。衰老相关的β-半乳糖苷酶活性，衰老相关的异染色质病灶，和p21经常检测到大细胞变化的领域。大细胞变化的肝细胞未显示增殖或凋亡活性。衰老特征的频繁表达和增殖或凋亡活性的缺乏表明大细胞变化代表衰老。在慢性B型肝炎中，大细胞改变和肝细胞癌的平行增加提高了细胞衰老作为防止恶性转化的保护措施而不是肝细胞癌的前兆的可能性。(C)2009 Elsevier Inc. All rights reserved.
Large cell change involves the clustering of hepatocytes with hyperchromatism and cellular enlargement without an increase in the nuclear/cytoplasmic ratio. This study investigated whether large cell change in chronic viral hepatitis reflects cellular senescence because of morphological similarities between the 2 conditions. The expression of markers of senescence such as senescence-associated beta-galactosidase, senescence-associated heterochromatic foci, and p21, as well as markers of cell kinetics such as Ki-67, was examined in 26 frozen and 82 formalin-fixed liver specimens. Large cell change was frequently detected in chronic hepatitis B cases with advanced histologic staging, particularly those with hepatocellular carcinoma. Senescence-associated beta-galactosidase activity, senescence-associated heterochromatic foci, and p21 were frequently detected in areas of large cell change. Hepatocytes with large cell change showed no proliferative or apoptotic activity. The frequent expression of senescent features and the absence of proliferative or apoptotic activity suggest that large cell change represents senescence. The parallel increase in large cell change and hepatocellular carcinoma in chronic hepatitis B raises the possibility that cellular senescence develops as a safeguard against malignant transformation rather than as a precursor of hepatocellular carcinoma. (C) 2009 Elsevier Inc. All rights reserved.