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DCP和Glypican-3在人HCC组织中的表达及临床意义
来源:吉林省四平市中心医院 | 作者:sjzxads | 发布时间:2013-12-6 访问人数: 198

DCP和Glypican-3在人HCC组织中的表达及临床意义

Expression of DCP and Glypican-3 in human hepatocellular cancer and its clinic significance


罗红1 李惠2 


1, 吉林省四平市中心医院病理科,吉林 四平 

2, 吉林省四平市中心医院消化内科,吉林 四平


Abstract

ABSTRACT:Objective To study the e­xpression of DCP and Glypican-3 in primary hepatocellular cancer (HCC) and the relationship with prognosis of HCC, and to provide new indicators for the prognosis of HCC.Methods Immunohistochemical way was used to study the e­xpression of DCP and Glypican-3 monoclonal antibody in HCC and control tissue(A total of 117 patients),as AFP was used as a control. SPSS17.0 was used to analyze the relationship between the e­xpression of the two kinds of protein and the clinical pathological features in HCC,and compare the e­xpression of different groups,and analyze the clinical and pathological features which may affect the survival prognosis of HCC from univariate and multivariate factors. Results The positive e­xpression rate of DCP, Glypican-3 and AFP in HCC were 74.32%, 63.51% and 51.35% respectively,and that of DCP and Glypican-3 in HCC was higher than that in adjacent tissue,and that was zero in normal liver tissue. The sensitivity,specificity and accuracy of the three kinds of protein e­xpression in HCC were all DCP>Glypican-3>AFP,and no correlation of each other(P>0.05).It was showed that three kinds of protein and preoperative serum AFP, tumor size, differentiation, intrahepatic metastasis, portal vein thrombosis were associated with early postoperative recurrence and death by Kaplan-Meier and univariate analysis,and the e­xpression of Glypican-3 and DCP in tumor tissue and portal vein thrombosis, tumor size of HCC were risk factors ,and were positively correlated of recurrence and death of HCC by COX regression analysis(P<0.05).Conclusion DCP and Glypican-3 were studied that whose e­xpression of in HCC tissue show high sensitivity and high specificity ,which consistent approximately with currently serological studies and are complementary with AFP in diagnosis and differential diagnosis of HCC, and are closely related to clinical- pathological features and biological behavior of HCC, can be used as an independent predictor of HCC prognosis.

KEY WORDS:HCC;DCP;Glypican-3;IHC;Diagnosis;Prognosis. 

摘要:目的 研究原发性肝细胞癌(HCC)组织中DCP、Glypican-3的表达情况及其与HCC预后的关系,为其血清学研究提供组织学依据,并为HCC的预后判断提供新的指标。方法 应用免疫组化方法研究DCP、Glypican-3在HCC及对照组织(n=117例)中的表达情况,以AFP作为对照,分析二种蛋白与HCC的临床、病理特征的关系,比较二者在不同组病例中的表达情况,并根据随访患者预后情况对HCC临床病理特点进行单因素及多因素分析。结果DCP、Glypican-3及AFP在HCC中阳性表达率分别为74.32%、63.51%、51.35%,前二者在HCC组织的阳性表达高于癌旁组织,在正常肝组织中均为阴性表达,其表达的敏感度、特异度和准确度均为DCP>Glypican-3>AFP,三者表达无相关性(P>0.05)。Kaplan-Meier分析及单因素分析显示:三种蛋白表达情况及术前血清AFP、肿瘤大小、分化程度、肝内转移、门脉癌栓均与术后早期复发死亡相关(P<0.05)。COX回归分析显示肿瘤组织中的Glypican-3及DCP的表达与门脉癌栓,肿瘤大小等因素为HCC术后复发死亡的危险因素,且与HCC的复发死亡均呈正相关(P<0.05)。结论 DCP、Glypican-3在HCC组织中有高敏感度和高特异度的表达, 与目前所研究的血清学结果基本一致,并与AFP在HCC诊断及鉴别诊断的应用上互为补充,与HCC的临床病理特点及生物学行为密切相关,均可以作为HCC预后判断的独立指标。

关键词 :原发性HCC;DCP;Glypican-3;免疫组化;诊断;预后

中图分类号:R445

0 引言

原发性肝细胞癌(HCC)是一种较常见且发病率较高的消化系统恶性肿瘤,特别在亚洲高发[1,2]。每年全世界逾50万人死于HCC [3]。HCC的早期诊断及预后判断尤为重要,而传统HCC预后判断较少提及肿瘤标志物,或仅做间接推断。有研究表明异常凝血酶原(Des-γ-Carboxy Prothrombin,DCP)和磷脂酰肌醇(Glypican-3)的血清表达与HCC分化程度密切相关,且二者在HCC的诊断上与AFP互补[4],但国内外对于二者研究多集中于血清学研究方面,缺少组织学研究结果支持。本文将以此为切入点,对原发性HCC组织中DCP和Glypican-3的表达情况及其临床意义进行研究。

1材料与方法

1.1材料

取2001年至2010年在四平市中心医院肝叶切除标本117例,术前均未行放疗或化疗,其中肝细胞癌74例(取自肿瘤内非坏死组织)、癌旁16例(取自病理诊断为HCC标本中距肿瘤1-2cm的肝脏组织)、其他肝病(包括肝硬化、肝胆管细胞癌、肝转移癌、肝囊肿、肝脓肿等,其中部分为穿刺活检标本)30例和外伤性肝破裂(正常肝)13例的组织蜡块(癌旁组不在总例数之内),其中男性89例,女性28例,男女比例为3.18:l,年龄25~73岁,平均年龄为48.65岁。 

DCP-抗(0.1ml浓缩液) 购自北京博奥森生物技术有限公司;Glypican-3 (6.0ml 工作液),AFP(6.0m1工作液)、PV9000试剂盒均购自北京中杉金桥生物科技公司;其余耗材为中国医科大学四平医院病理科馈赠。

1.2方法

调查患者术前血清学检查情况(AFP等)、肿瘤大小、一般状况等,将自2001年至2006年HCC病例共49例进行随访,5年(60个月)为截尾时间,调查其生存时间及生存质量等。对每个标本行连续切片,厚3μm。用DCP和Glypican-3单克隆抗体对每组组织切片进行免疫组化染色,将AFP单克隆抗体对照研究,以PBS代替一抗作为阴性对照,采用IHS法对其着色强度及阳性细胞率进行评分。统计工作由SPSS17. 0软件完成,检验水准α= 0. 05。

2结果

2.1 HCC组及癌旁组DCP、Glypican-3及AFP的表达

三种蛋白在74例HCC组织和16例癌旁组织中均有不同程度阳性表达,而在正常肝组织中均为阴性表达,三者均为细胞浆表达,AFP可见部分细胞膜表达。DCP在癌巢中心表达强于周围,阳性程度与细胞异形大小程度无明显相关;Glypican-3在癌巢周围表达强于中心,细胞异形越大的癌细胞表达更强(图1)。其中DCP与Glypican-3在HCC组织的表达强于癌旁组织,其差异有统计学意义(P<0.05),而两种组织中AFP的表达情况无明显差异(P>0.05)(表1)。DCP、Glypican-3及AFP在HCC组织的表达的阳性率分别为74.32%(55/74)、63.51%(47/74)和51.35%(38/74)。(表1)

表1 HCC组织中DCP、Glypican-3及AFP表达情况 例(%)

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