Karamitopoulou Eva, Tornillo Luigi, Zlobec Inti, Cioccari Lukas, Carafa Vincenza, Borner Markus, Schaffner Thomas, Brunner Thomas, Diamantis Ioannis, Zimmermann Arthur, Terracciano Luigi
Institutes of Pathology, University of Basel, Basel, Switzerland Second Department of Pathology, University of Athens, Haidari, Athens, Greece.
Am J Clin Pathol. 2008 Nov;130(5):780-6. doi: 10.1309/AJCP35FDCAVANWMM.
Cholangiocarcinoma is the second most common malignant tumor of the liver. We analyzed, immunohistochemically, the significance of cell cycle- and apoptosis-related markers in 128 cholangiocarcinomas (42 intrahepatic, 70 extrahepatic, and 16 gallbladder carcinomas) combined in a tissue microarray. Follow-up was available for 57 patients (44.5%). In comparison with normal tissue (29 specimens), cholangiocarcinomas expressed significantly more frequently p53, bcl-2, bax, and COX-2 (P.05 <). Intrahepatic tumors were significantly more frequently bcl-2+ and p16+, whereas extrahepatic tumors were more often p53+ (P < .05). Loss of p16 expression was associated with reduced survival of patients. Our data show that p53, bcl-2, bax, and COX-2 have an important role in the pathogenesis of cholangiocarcinomas. The differential expression of p16, bcl-2, and p53 between intrahepatic and extrahepatic tumors demonstrates that there are location-related differences in the phenotype and the genetic profiles of these tumors. Moreover, p16 was identified as an important prognostic marker in cholangiocarcinomas.
胆管癌是肝脏第二常见的恶性肿瘤。我们通过免疫组织化学方法分析了组织芯片中128例胆管癌(42例肝内胆管癌、70例肝外胆管癌和16例胆囊癌)中细胞周期和凋亡相关标志物的意义。57例患者(44.5%)有随访资料。与正常组织(29个标本)相比,胆管癌中p53、bcl-2、bax和COX-2的表达明显更频繁(P<0.05)。肝内肿瘤bcl-2+和p16+的比例明显更高,而肝外肿瘤p53+的比例更高(P<0.05)。p16表达缺失与患者生存率降低相关。我们的数据表明,p53、bcl-2、bax和COX-2在胆管癌的发病机制中起重要作用。肝内和肝外肿瘤之间p16、bcl-2和p53的差异表达表明,这些肿瘤在表型和基因谱方面存在位置相关差异。此外,p16被确定为胆管癌的一个重要预后标志物。