目的探讨肝脏祖细胞标志物c-kit在人肝硬化及肝细胞肝癌(HCC)组织中的表达及其与临床病理特征的关系。方法对30例肝硬化、40例肝细胞肝癌标本及3例正常组织标本进行常规组织学观察以及c-kit、CD45免疫组化染色,对肿瘤细胞的分化程度及肝硬化组织门静脉炎症程度进行分型和评分,分析c-kit表达与肝硬化及肝细胞肝癌的临床病理特征的联系。结果正常肝脏中c-kit染色阴性。20/30例肝硬化中发现c-kit(+)细胞,位于门脉周围区域和纤维间隔内,个别阳性细胞整合到成熟胆管,肝硬化结节中没有发现c-kit(+)细胞。19/40例HCC组织中存在c-kit (+)肿瘤细胞,在肿瘤细胞之间或肿瘤结节周围分散分布。HBsAg及Anti-HBc在c-kit(+)与c-kit (-)HCC之间表达有显著性差异(χ^2=5.063,P〈0.05;χ^2=6.667,P〈0.05)。c-kit表达与肿瘤的分化程度紧密相关(χ^2=10.384,P〈0.05),分化程度越低,c-kit表达越高。结论骨髓来源的肝脏祖细胞参与了部分肝硬化病变过程中的肝再生及HCC的形成和发展,c-kit表达情况对于判断HCC预后有一定意义。
Objective To investigate the expression of hepatic progenitor cell marker c-kit and to explore the relationship between the c-kit expression and the clinicopathologic features in human liver cirrhosis and hepatocellular carcinoma. Methods Surgical specimens from 30 cases of human liver cirrhosis, 40 cases of human hepatocellular carcinoma and 3 cases of normal liver were investigated by HE and immunohistochemical staining for c-kit and CD45. The stages of tumor cell differentiation and the degree of portal inflammation were assessed. Results In normal liver c-kit was negative. Immunostaining for c-kit was detected in the periportal region and fibrous septa in 20 of 30 liver cirrhosis. Very few c-kit-positive cells were found integrated into bile duct. There were no c-kit ( + ) cells in the liver cirrhosis nodules. We found c-kit( + ) tumor cells scattered individually among the tumor cells or located in the periphery of tumor nodules in 19 of 40 HCC. There were significant differences in the expression of HBsAg and Anti-HBc between the c-kit ( + ) HCC and c-kit ( - ) HCC ( χ^2 = 5. 063, P 〈 0. 05 ; χ^2 = 6. 667, P 〈 0. 05 ). The c-kit expression was closely related to the degree of tumor cell differentiation ( χ^2 = 10. 384, P 〈 0. 05 ), and it was more often seen in the HCC of poor tumor cell differentiation. Conclusion Bone marrow derived hepatic progenitor cells were involved in the liver regeneration during the course of liver cirrhosis and the pathogenesis and development of HCC. C-kit expression may be a prognostic indicator for HCC.