Charlotte F, L'Herminé A, Martin N, Geleyn Y, Nollet M, Gaulard P, Zafrani E S
Service d'Anatomie et de Cytologie Pathologiques, Hôpital Henri Mondor, Créteil, France.
Am J Pathol. 1994 Mar;144(3):460-5.
The bcl-2 protein, which prolongs cell survival by blocking apoptosis, is expressed by progenitor cells in several self-renewing tissues and by tumoral cells in some extrahepatic neoplasms. Because the liver is a slow self-renewing tissue, an immunohistochemical study of the cellular distribution of the bcl-2 protein was performed in normal liver (12 cases), nontumoral hepatic lesions (33 cases), and benign or malignant liver tumors (46 cases). In normal liver, bcl-2 was expressed by bile ductules and small bile duct epithelium, but not by hepatocytes or large bile duct epithelium. In cirrhosis and focal nodular hyperplasia, epithelial cells of the ductular proliferation were bcl-2-positive. Eight of 11 cholangiocarcinomas stained positively for bcl-2, whereas all 15 hepatocellular carcinomas were bcl-2-negative. bcl-2 was also expressed in 6 of 14 metastatic adenocarcinomas. These findings suggest that the ductular cells and small bile duct epithelial cells might have a prolonged survival and might be hepatic progenitor cells. In addition, the bcl-2 protein appears to be a marker of cholangiocarcinoma but not of hepatocellular carcinoma and could help in distinguishing between these two primary liver tumors.
bcl-2蛋白可通过阻断细胞凋亡来延长细胞存活时间，在几种自我更新组织的祖细胞以及一些肝外肿瘤的肿瘤细胞中表达。由于肝脏是一种自我更新缓慢的组织，因此对12例正常肝脏、33例非肿瘤性肝病变以及46例良性或恶性肝肿瘤进行了bcl-2蛋白细胞分布的免疫组化研究。在正常肝脏中，bcl-2在胆小管和小胆管上皮细胞中表达，但在肝细胞或大胆管上皮细胞中不表达。在肝硬化和局灶性结节性增生中，增生的小胆管上皮细胞bcl-2呈阳性。11例胆管癌中有8例bcl-2染色阳性，而15例肝细胞癌均为bcl-2阴性。14例转移性腺癌中有6例也表达bcl-2。这些发现表明，小胆管细胞和小胆管上皮细胞可能具有延长的存活时间，可能是肝祖细胞。此外，bcl-2蛋白似乎是胆管癌的标志物，而不是肝细胞癌的标志物，有助于区分这两种原发性肝癌。
