Aishima Shin-Ichi, Asayama Yoshiki, Taguchi Ken-Ichi, Sugimachi Keishi, Shirabe Ken, Shimada Mitsuo, Sugimachi Keizo, Tsuneyoshi Masazumi
Department of Anatomic Pathology and of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Mod Pathol. 2002 Nov;15(11):1181-90. doi: 10.1097/01.MP.0000032537.82380.69.
The cytokeratins phenotype is largely preserved during neoplastic transformation and tumor development. We evaluated the immunoreactivity of biliary epithelial markers keratin 903 and cytokeratin 7 and 19 for intrahepatic cholangiocarcinoma, and compared the results with those for biliary dysplasia and hepatocellular carcinoma. Reactivity with keratin 903 was weakly expressed and increased after the expression of cytokeratin 7 and 19 during human intrahepatic bile duct development. More than 80% of cases of biliary dysplasia showed positive reactivity with keratin 903. Of the 30 cases of hepatocellular carcinoma, 3 (10%), 6 (20%), and 1 (3%) showed positive reactivity with Keratin 903 and cytokeratin 7 and 19, respectively. Among the 73 cases of intrahepatic cholangiocarcinoma, 54 (74%), 66 (90%), and 61 (84%) showed positive reactivity with keratin 903 and cytokeratin 7 and 19, respectively. On clinicopathologic examination of intrahepatic cholangiocarcinomas, reduced keratin 903 reactivity was significantly higher in tumors with an expansive growth pattern (P <.0001), in those with medullary-type stromal reaction (P =.0327), in those without perineural invasion (P =.0001), and in those without lymph node metastasis (P =.0015). In addition, the reactivity with Keratin 903 was directly correlated with expression of cytokeratin 7 and 19 (P =.0153 and P <.0001, respectively). Cases showing reduced keratin 903 reactivity were characterized by a distinctive morphology indicating an hepatocellular carcinoma-like pattern. Multivariate analysis of overall survival revealed that keratin 903 reactivity was a significantly independent prognostic factor. In conclusion, patients with intrahepatic cholangiocarcinoma showing reduced keratin 903 reactivity had a favorable prognosis. Remarkably, the cytokeratin phenotype of intrahepatic cholangiocarcinoma was correlated with the morphologic appearance of intrahepatic cholangiocarcinoma.
细胞角蛋白表型在肿瘤转化和肿瘤发展过程中基本保持不变。我们评估了胆管上皮标志物角蛋白903、细胞角蛋白7和19在肝内胆管癌中的免疫反应性，并将结果与胆管发育异常和肝细胞癌的结果进行比较。在人类肝内胆管发育过程中，角蛋白903的反应性表达较弱，在细胞角蛋白7和19表达后增加。超过80%的胆管发育异常病例对角蛋白903呈阳性反应。在30例肝细胞癌病例中，分别有3例（10%）、6例（20%）和1例（3%）对角蛋白903、细胞角蛋白7和19呈阳性反应。在73例肝内胆管癌病例中，分别有54例（74%）、66例（90%）和61例（84%）对角蛋白903、细胞角蛋白7和19呈阳性反应。在对肝内胆管癌进行临床病理检查时，在具有膨胀性生长模式的肿瘤中（P<.0001）、具有髓样型基质反应的肿瘤中（P=.0327）、无神经周围侵犯的肿瘤中（P=.0001）以及无淋巴结转移的肿瘤中（P=.0015），角蛋白903反应性降低的比例显著更高。此外，角蛋白903的反应性与细胞角蛋白7和19的表达直接相关（分别为P=.0153和P<.0001）。角蛋白903反应性降低的病例具有独特的形态，表现为肝细胞癌样模式。对总生存期的多变量分析显示，角蛋白903反应性是一个显著的独立预后因素。总之，肝内胆管癌患者角蛋白903反应性降低预后良好。值得注意的是，肝内胆管癌的细胞角蛋白表型与肝内胆管癌的形态学表现相关。
