CK19和GPC3的表达与肝移植术后肝细胞癌复发的相关性

Correlation between recurrence of prinmry hepatocellular carcinoma after liver transplantation and expression of CK19 and GPC-3

目的比较不同细胞角蛋白19（Cytokeratin-19，CK19）和磷脂酰肌醇蛋白聚糖3（Glypican-3，GPC3）免疫表型肝细胞癌患者间肝移植术后肿瘤复发的差异。方法选择2005年5月20日至2014年9月15Et间因原发性肝细胞癌接受肝移植的130例受者，回顾性分析受者的临床资料。术后对所有受者进行随访，随访截止至2015年4月15日，随访时间中位数为29个月（1-90个月）。术中获取所有受者的病肝组织，进行HE染色及CK19和GPC3免疫组织化学染色，于光镜下观察病肝组织病理改变及CK19和GPC3表达情况；采用LogRank法对肝癌复发受者的预后差异及比较进行单因素分析，对可能影响受者预后的单因素进行Cox回归模型多因素分析。结果根据肝细胞癌CK19和GPC3检测结果的不同，将受者分为CK19＋GPC3＋组、CK19-GPC3＋组和CK19-GPC3-组，3组分别有23例（17．7％）、65例（50％）和42例（32．3％）受者。术后共64例受者发生肿瘤复发，其中CK19＋GPC3＋组复发14例，复发率为60．9％，复发时间为术后1～76个月；CK19-GPC3＋组37例，复发率为56．9％，复发时间为术后1～77个月；CK19-GPC3-组13例，复发率为31．0％，复发时间为术后4～90个月；3组间肿瘤复发率的比较，差异均有统计学意义（P〈0．05）；CK19＋GPC3＋组、CK19-GFC3＋组分别与CK19-GPC3-组间肿瘤复发时间的差异有统计学意义（P〈0．017），而CK19＋GPC3＋组与CK19-GPC3＋组间的差异无统计学意义（P〉0．05）。3组间肿瘤复发受者的年龄、甲胎蛋白水平以及肿瘤分化程度和TNM分期的差异均有统计学意义（P〈0．05）。Cox多因素分析结果显示，TNM分期及CK19和GPC3分组是影响预后的重要独立因素（P〈0．05）。结论不同肝细胞癌CK19和GPC3免疫表型患者肝移植术后的肿瘤复发与基于CK19和GPC3分子分型密切相关。

Objective To investigate the correlation between recurrence of the primary hepatocellular carcinoma （HCC） after liver transplantation and the expression of CK19 and GPC3. Method The clinical and pathological data of 130 cases of liver transplant patients in You An Hospital, Capital Medical University due to HCC from May 20, 2005 to September 15, 2014 were retrospectively analyzed. The mean follow-up time was 28 months （range, 1 to 90 months） after liver transplantation. During liver transplantation, the liver tissues of all the recipients were obtained for HE staining and immunohistochemical staining for CK19 and GPC3. The pathological changes and expression of CK19 and GPC3 were observed under the light microscopy. All cases were followed up. Kaplan-Meier and Cox method was used to analyze the relapse of patients. Result In 130 cases of liver transplant patients collected, 64 cases of recurrence occurred. Based on the expression of GPC3 and CK19 staining, the recurrent cases were divided into three groups： CK19＋ GPC3＋ phenotype （23 cases, 17.7%）, CK19-GPC3＋ phenotype （65 cases, 50%）, and CK19-GPC3- phenotype （42 cases, 32. 3%）. There were 14 cases of recurrence in CK19＋ GPC3＋ （60. 9%, recurrence time of 1 to 76 months after operation）, 37 in CK19- GPC3＋ （56. 9%, recurrence time of 1 to 77 months afteroperation）, and 13 in CK19 GPC3- （31.0%, recurrence time of 4 to 90 months after operation）. There was significant difference among the 3 groups （P〈0. 05）. The recurrence time after operation in CK19＋ GPC3＋ group and CK19- GPC3＋ group was earlier than in CK19- GPC3- group （P〈0. 017）, and there was no significant difference between CK19＋ GPC3＋ group and CK19- GPC3＋ group. CK19/GPC3 grouping was an independent risk prognostic factor. Conclusion The recurrence of HCC patients after liver transplantation was closely correlated with the expression of CK19 and GPC3 in tumor cells.