肝细胞癌p53、E-cadherin和ki-67蛋白表达与肝切除术后预后的关系
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摘要
目的：研究p53、E-cadherin和ki-67蛋白在肝细胞癌(hepatocellular carcinoma, HCC)组织中的表达及与HCC临床病理指标和肝切除术后病人预后的关系。
方法：(1)应用组织芯片技术和免疫组织化学PV-6000两步法检测255例HCC组织标本、81例癌旁组织标本和79例肝硬化组织标本中p53、E-cadherin和ki-67蛋白的表达。(2)三种蛋白表达与HCC患者临床病理指标、肿瘤1年复发率和术后总生存期的关系。应用SPSS13.0统计软件,定性资料用χ2和pearson相关分析,生存分析用Kaplan-Meier和Log-rank检验.将可能对预后有影响的指标,引入Cox回归模型。取P<0.05为显著性检验水准对资料进行分析。
结果：(1)p53蛋白在HCC组织中表达阳性率为21.20%,在癌旁和肝硬化组织中不表达,差别有统计学意义(χ2=38.956,P=0.000)；p53阳性表达率在低分化的HCC组织中较高(χ2=6.403；P=0.011)；p53表达阳性组术后平均生存期为43.793个月,表达阴性组为53.406个月,两组差异有统计学意义(χ2=4.298；P=0.038)。(2)E-cadherin蛋白在HCC、癌旁和肝硬化组织中表达的阳性率为1.7.86%、9.88%和22.78%,在HCC组织和癌旁组织中的表达差别无统计意义(χ2=2.917；P=0.088),在HCC组织和肝硬化组织中的表达差别无统计意义(χ2=0.948；P=0.330),在癌旁组织和肝硬化组织中的表达差别有统计意义(χ2=4.897,P=0.027)。E-cadherin阳性表达组的HCC肿瘤直径小于阴性表达组(χ2=4.658；P=0.031),阴性表达组1年复发率明显高于阳性组(χ2=5.699；P=0.017)。(3)ki-67蛋白在HCC组织中表达阳性率为31.76%,在癌旁和肝硬化组织中均不表达,差别有统计学意义(χ2=63.149；P=0.000)。ki-67阳性表达率在伴有血管癌栓的HCC组织中比不伴癌栓组高(χ2=4.442,P=0.035),在低分化HCC组织中比高中分化组织高(χ2=7.589；P=0.006),差异有统计意义,阳性表达组与阴性表达组相比1年复发率高(χ2=9.852；P=0.002),ki-67表达阳性组术后平均生存期为38.004个月,表达阴性组为55.168个月,两组差异有统计意义(χ2=9.775；P=0.002)。(4)三种蛋白表达的相关分析表明,p53与ki-67的表达呈正相关(r=0.148,P=0.019),与E-cadherin呈负相关(r=-0.163,P=0.010)。(5)Cox回归多因素分析显示,ki-67是HCC肝切除术后独立的风险预后因子。
结论：(1)E-cadherin蛋白阴性表达者和ki-67蛋白阳性表达者早期复发率高。(2)p53可以作为评估HCC肝切除术后预后的指标之一。(3)ki-67是HCC肝切除术后独立的风险预后因子。
Objective To study the expressions of p53, E-cadherin and ki-67 in the tissues of heatocellular carcinoma (HCC) and the relationships between them and clinical pathology and the prognosis of patients with HCC after hepatectomy.
Methods (1)The expressions of p53, E-cadherin and ki-67 in 255 patients with HCC,81 cases with adjacent non-cancerous tissues and 79 cases with cirrhotic tissues were examined by tissue microarray and immunohistochemistry PV-6000 methods. (2) The relationships between their expressions and clinical pathological data,1-year recurrent rate and overall survival after hepatectomy were analyzed. (3) The data were analyzed by software SPSS 13.0,χ2-test, Pearson correlation test and Cox proportional hazard model was used, P<0.05 was considered as level of a test.
Results (1) The expression rate of p53 protein in HCC tissues was 21.20%, there was not expressed in adjacent non-cancerous tissues and cirrhotic tissues (χ2=38.956,P=0.000). A significant correlation was found between the expression of p53 and the differentiation of the tumor tissue (χ2=6.403,P=0.011), and the overall survival of the patients with p53 positive expression was shorter than the negative(χ2=4.298;P=0.038). (2) The expression rate of E-cadherin protein in HCC, adjacent non-cancerous tissues and cirrhotic tissues was 17.86%,9.88% and 22.78%, and there was not significant difference between HCC tissues and adjacent non-cancerous (χ2=2.917,P=0.088) and cirrhotic tissues (χ2=0.948, P=0.330), but a significant difference between the expression of E-cadherin in adjacent non-cancerous and cirrhotic tissues(χ2=4.897,P=0.027). The expression of E-cadherin in HCC reversely correlated with the tumor size(χ2=4.658; P=0.031), and the 1-year HCC recurrent rate in patients with positive expression was higher than the negative(χ2=5.699,P=0.017). (3) The expression rate of ki-67 protein in HCC tissue was 31.76%, but it was not expressed in adjacent non-cancerous tissues and cirrhotic tissues (χ2=63.149, P=0.000). The expression of ki-67 correlated with vascular invasion (χ2=4.442, P=0.035) and the differentiation of the tumor (χ2=7.589, P=0.006), the higher 1-year recurrent rate (χ2=9.852, P=0.002) and the shorter overall survival (χ2=9.775, P=0.002) was seen in the positive group than the negative. (4) The expression of p53 was positivly correlated with ki-67 (r=0.148, P=0.019), negatively with E-cadherin (r=-0.163, P=0.010). (5) Multivariant Cox regression analysis showed that the expression of ki-67 was a independent factor of prognosis.
Conclusions (1) The negative expression of E-cadherin and the positive expression of ki-67 would predict the higher recurrent rate of early stage. (2) The expression of p53 was one of the indicators to evaluate the prognosis of patients with HCC after hepatectomy. (3)ki-67 was a independent factors of prognosis of patients with HCC after hepatectomy.
方法：(1)应用组织芯片技术和免疫组织化学PV-6000两步法检测255例HCC组织标本、81例癌旁组织标本和79例肝硬化组织标本中p53、E-cadherin和ki-67蛋白的表达。(2)三种蛋白表达与HCC患者临床病理指标、肿瘤1年复发率和术后总生存期的关系。应用SPSS13.0统计软件,定性资料用χ2和pearson相关分析,生存分析用Kaplan-Meier和Log-rank检验.将可能对预后有影响的指标,引入Cox回归模型。取P<0.05为显著性检验水准对资料进行分析。
结果：(1)p53蛋白在HCC组织中表达阳性率为21.20%,在癌旁和肝硬化组织中不表达,差别有统计学意义(χ2=38.956,P=0.000)；p53阳性表达率在低分化的HCC组织中较高(χ2=6.403；P=0.011)；p53表达阳性组术后平均生存期为43.793个月,表达阴性组为53.406个月,两组差异有统计学意义(χ2=4.298；P=0.038)。(2)E-cadherin蛋白在HCC、癌旁和肝硬化组织中表达的阳性率为1.7.86%、9.88%和22.78%,在HCC组织和癌旁组织中的表达差别无统计意义(χ2=2.917；P=0.088),在HCC组织和肝硬化组织中的表达差别无统计意义(χ2=0.948；P=0.330),在癌旁组织和肝硬化组织中的表达差别有统计意义(χ2=4.897,P=0.027)。E-cadherin阳性表达组的HCC肿瘤直径小于阴性表达组(χ2=4.658；P=0.031),阴性表达组1年复发率明显高于阳性组(χ2=5.699；P=0.017)。(3)ki-67蛋白在HCC组织中表达阳性率为31.76%,在癌旁和肝硬化组织中均不表达,差别有统计学意义(χ2=63.149；P=0.000)。ki-67阳性表达率在伴有血管癌栓的HCC组织中比不伴癌栓组高(χ2=4.442,P=0.035),在低分化HCC组织中比高中分化组织高(χ2=7.589；P=0.006),差异有统计意义,阳性表达组与阴性表达组相比1年复发率高(χ2=9.852；P=0.002),ki-67表达阳性组术后平均生存期为38.004个月,表达阴性组为55.168个月,两组差异有统计意义(χ2=9.775；P=0.002)。(4)三种蛋白表达的相关分析表明,p53与ki-67的表达呈正相关(r=0.148,P=0.019),与E-cadherin呈负相关(r=-0.163,P=0.010)。(5)Cox回归多因素分析显示,ki-67是HCC肝切除术后独立的风险预后因子。
结论：(1)E-cadherin蛋白阴性表达者和ki-67蛋白阳性表达者早期复发率高。(2)p53可以作为评估HCC肝切除术后预后的指标之一。(3)ki-67是HCC肝切除术后独立的风险预后因子。
Objective To study the expressions of p53, E-cadherin and ki-67 in the tissues of heatocellular carcinoma (HCC) and the relationships between them and clinical pathology and the prognosis of patients with HCC after hepatectomy.
Methods (1)The expressions of p53, E-cadherin and ki-67 in 255 patients with HCC,81 cases with adjacent non-cancerous tissues and 79 cases with cirrhotic tissues were examined by tissue microarray and immunohistochemistry PV-6000 methods. (2) The relationships between their expressions and clinical pathological data,1-year recurrent rate and overall survival after hepatectomy were analyzed. (3) The data were analyzed by software SPSS 13.0,χ2-test, Pearson correlation test and Cox proportional hazard model was used, P<0.05 was considered as level of a test.
Results (1) The expression rate of p53 protein in HCC tissues was 21.20%, there was not expressed in adjacent non-cancerous tissues and cirrhotic tissues (χ2=38.956,P=0.000). A significant correlation was found between the expression of p53 and the differentiation of the tumor tissue (χ2=6.403,P=0.011), and the overall survival of the patients with p53 positive expression was shorter than the negative(χ2=4.298;P=0.038). (2) The expression rate of E-cadherin protein in HCC, adjacent non-cancerous tissues and cirrhotic tissues was 17.86%,9.88% and 22.78%, and there was not significant difference between HCC tissues and adjacent non-cancerous (χ2=2.917,P=0.088) and cirrhotic tissues (χ2=0.948, P=0.330), but a significant difference between the expression of E-cadherin in adjacent non-cancerous and cirrhotic tissues(χ2=4.897,P=0.027). The expression of E-cadherin in HCC reversely correlated with the tumor size(χ2=4.658; P=0.031), and the 1-year HCC recurrent rate in patients with positive expression was higher than the negative(χ2=5.699,P=0.017). (3) The expression rate of ki-67 protein in HCC tissue was 31.76%, but it was not expressed in adjacent non-cancerous tissues and cirrhotic tissues (χ2=63.149, P=0.000). The expression of ki-67 correlated with vascular invasion (χ2=4.442, P=0.035) and the differentiation of the tumor (χ2=7.589, P=0.006), the higher 1-year recurrent rate (χ2=9.852, P=0.002) and the shorter overall survival (χ2=9.775, P=0.002) was seen in the positive group than the negative. (4) The expression of p53 was positivly correlated with ki-67 (r=0.148, P=0.019), negatively with E-cadherin (r=-0.163, P=0.010). (5) Multivariant Cox regression analysis showed that the expression of ki-67 was a independent factor of prognosis.
Conclusions (1) The negative expression of E-cadherin and the positive expression of ki-67 would predict the higher recurrent rate of early stage. (2) The expression of p53 was one of the indicators to evaluate the prognosis of patients with HCC after hepatectomy. (3)ki-67 was a independent factors of prognosis of patients with HCC after hepatectomy.
引文
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41.Osada T, SakamotoM, Ino Y, et al. E-cadherin is involved in the intrahepatic metastasis of hepatocellular carcinoma [J]. Hepatology,1996,24 (6):1460-1467.
42.李忠峰,郑建盛,林建生.Bax蛋白及Ki-67抗原在胆囊腺癌中的表达及相关性研究[J].中国医师进修杂志,2007,30(8)：4-7.
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44.陈壮威,戴起宝,兰斌,等.Plkl、Raf-1和ki-67在胃癌组织中的表达及其意义[J].福建医科大学学报,2009,43(2)：121-124.
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