凝集素捕获微量离心柱法检测甲胎蛋白异质体在原发性肝癌中的应用评价

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季君, 顾星, 高致远, 孙小娟, 董桂玲, 周军, 陈建栋, 高春芳. 凝集素捕获微量离心柱法检测甲胎蛋白异质体在原发性肝癌中的应用评价. 2011, 26(4): 256-259
JI Jun, GU Xing, GAO Zhiyuan, SUN Xiaojuan, DONG Guiling, ZHOU Jun, CHEN Jiandong, GAO Chunfang. Application evaluation of alpha-fetoprotein variant with lectin microcentrifugalcolumn method in the diagnosis of primary liver carcinoma. Labratory Medicine, 2011, 26(4): 256-259 复制到剪切板

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凝集素捕获微量离心柱法检测甲胎蛋白异质体在原发性肝癌中的应用评价

季君, 顾星, 高致远, 孙小娟, 董桂玲, 周军, 陈建栋, 高春芳

第二军医大学附属东方肝胆外科医院实验诊断科,上海 200438

作者简介:季君,女,1984年生,学士,主要从事肝癌的糖组学研究。

通讯作者:高春芳,联系电话:021-81875131。

摘要

目的

探讨凝集素捕获微量离心柱法检测甲胎蛋白异质体(AFP-L3)在原发性肝癌(PLC)中的临床应用。

方法

采用电化学发光法(ECL)和凝集素捕获微量离心柱法分别定量检测622例甲胎蛋白(AFP)阳性PLC、24例AFP阴性PLC、17例AFP阳性良性肝脏疾病患者AFP-L3,并比较凝集素捕获微量离心柱法和凝集素亲和免疫电泳自显影法检测AFP-L3的符合率。

结果

622例AFP阳性PLC患者中,AFP-L3阳性患者的γ-谷氨酰基转移酶(GGT)、总胆红素(TBil)明显高于AFP-L3阴性患者( P<0.05)。AFP-L3与患者的丙氨酸氨基转移酶(ALT)、白蛋白(Alb)均无相关性。凝集素捕获微量离心柱法和凝集素亲和免疫电泳自显影法检测AFP-L3的阳性率分别是46%、50%,两者的符合率为92%。按AFP浓度分层分析AFP-L3阳性率后发现,随AFP浓度升高,AFP-L3阳性呈现上升趋势。AFP-L3在AFP阳性的PLC患者和AFP阳性的良性肝脏疾病患者中的检出率分别为16.67%、23.53%,显著低于AFP阳性的PLC患者(63.5%, P<0.05)。

结论

凝集素捕获微量离心柱法与凝集素亲和免疫电泳自显影法具有较好的一致性; AFP-L3在AFP阳性的PLC患者中有较高的检出率,对临床具有辅助诊断和鉴别诊断价值。

关键词: 甲胎蛋白异质体; 凝集素捕获微量离心柱法; 原发性肝癌; 诊断

中图分类号:R446.62 文献标志码:A 文章编号:1673-8640(2011)04-0256-04

Application evaluation of alpha-fetoprotein variant with lectin microcentrifugalcolumn method in the diagnosis of primary liver carcinoma

JI Jun, GU Xing, GAO Zhiyuan, SUN Xiaojuan, DONG Guiling, ZHOU Jun, CHEN Jiandong, GAO Chunfang

Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China

Abstract

Objective

To investigate the clinical application of lectin microcentrifugalcolumn method for the measurement of alpha-fetoprotein variant(AFP-L3) in primary liver carcinoma(PLC).

Methods

Serum AFP-L3 in 622 AFP-positive PLC patients, 24 AFP-negative PLC patients and 17 AFP-positive patients with benign liver disease were quantitatively detected by electrochemiluminescence(ECL) method and lectin microcentrifugalcolumn method. The coincidence of AFP-L3 between lectin microcentrifugalcolumn method and lectin affinity immunoelectrophoresis autoradiography method was compared.

Results

In 622 AFP-positive PLC patients,there was no association of AFP-L3 with their clinical and biochemical indicators such as alanine aminotransferase(ALT) and albumin(Alb). In AFP-L3 positive group,the levels of gamma-glutamyltransferase (GGT) and total bilirubin(TBil)were much higher than those in AFP-L3 negative group( P<0.05). The AFP-L3 positive rates of lectin microcentrifugalcolumn method and lectin affinity immunoelectrophoresis autoradiography method were 46% and 50% respectively.The coincidence of the 2 methods was 92%. Stratified analysis by AFP concentration of AFP-L3 positive rate showed that the positive rate of AFP-L3 increased with the rising of AFP concentration. In AFP-negative PLC patients and AFP-positive patients with benign liver diseases, the AFP-L3 positive rates were 16.67% and 23.53% respectively, which were obviously lower than those of AFP-positive PLC patients (63.5%, P<0.05).

Conclusions

Lectin microcentrifugalcolumn method is consistent with lectin affinity immunoelectrophoresis autoradiography method. In AFP-positive PLC patients, the detection rate of AFP-L3 is higher, and AFP-L3 has a clinical value in the auxiliary diagnosis and differential diagnosis.

Keyword: Alpha-fetoprotein variant; Lectin microcentrifugalcolumn method; Primary liver carcinoma; Diagnosis

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引言

虽然甲胎蛋白(AFP)是目前公认的原发性肝癌(PLC)的肿瘤标志物, 广泛应用于肝癌的早期辅助诊断、疗效判断和预测复发中^[1], 但因其敏感性和特异性均不够理想^[2~4], 迫切需要有更好的指标。研究发现肝病伴随多种蛋白异常糖基化^[5], 在不同生理病理状态下产生不同的糖链结构, 且具有肿瘤特异性。其中AFP糖蛋白依据与小扁豆凝集素(LCA)的亲和力分为3种类型。甲胎蛋白异质体1(AFP-L1)不与LCA结合, 主要出现在良性肝脏疾病中。甲胎蛋白异质体2(AFP-L2)与LCA有一定的亲和力, 多由卵黄囊瘤产生, 孕妇血清中也能检测到。甲胎蛋白异质体3(AFP-L3)与LCA有结合活性, 主要由肿瘤细胞产生^[6]。有报道称, 在产AFP的PLC患者中, AFP-L3的阳性率高达60%, 但在慢性肝脏疾病中阳性率< 5%^[7]。AFP-L3已于2005年被美国食品与药品监督管理局(FDA)批准为PLC的肿瘤标志物^[8]。以往AFP-L3的检测方法由于存在试剂昂贵、操作繁琐等缺点, 迄今没有在临床广泛使用。本研究采用国内新研制的凝集素捕获微量离心柱法对622例AFP阳性PLC、24例AFP阴性PLC、17例AFP阳性良性肝脏疾病患者的AFP-L3进行检测, 其中50例PLC患者分别用凝集素捕获微量离心柱法和凝集素亲和免疫电泳自显影法对AFP-L3的阳性检出率进行了比较, 以期评价凝集素捕获微量离心柱法检测AFP-L3在PLC诊断及鉴别诊断中的价值。

材料和方法

一、研究对象

共选取663例患者。其中646例PLC患者为2009年10月至2010年4月间来东方肝胆外科医院就诊, 根据影像或病理确诊, 诊断标准符合《新编常见恶性肿瘤诊治规范》中有关PLC的诊断标准。这些PLC患者中有622例AFP阳性(AFP> 20 μ g/L), 其中男545例, 平均年龄51.4岁, 女77例, 平均年龄55.8岁; 24例AFP阴性(AFP为10~20 μ g/L), 其中男20例, 平均年龄50.9岁, 女4例, 平均年龄65.8岁。另有由长征医院感染科提供AFP阳性(AFP> 20 μ g/L)的良性肝脏疾病患者17例, 其中肝硬化7例, 慢性乙型肝炎4例, 慢性重症肝炎6例。所有血清标本均采自患者诊断明确且尚未接受介入或手术治疗前, 分离后保存于-80 ℃超低温冰箱备用。

二、观察指标

以血清AFP、AFP-L3、γ -谷氨酰基转移酶(GGT)、丙氨酸氨基转移酶(ALT)、总胆红素(TBil)、白蛋白(Alb)为观察指标。以血清AFP> 20 μ g/L、AFP-L3≥ 10%作为阳性判断标准。

三、检测方法

AFP应用电化学发光法(ECL), 检测试剂为罗氏公司的AFP Modular E170专用试剂盒, 仪器为罗氏E170电化学发光分析系统。

AFP-L3检测试剂为北京热景生物技术有限公司提供的AFP-L3亲和吸附离心管。凝集素亲和免疫电泳自显影法由东方肝胆外科医院分子肿瘤实验室检测。凝集素捕获微量离心柱法的具体操作参照说明书进行, 主要检测原理为AFP-L3亲和吸附离心管中预装有亲和介质LCA, 能特异性结合AFP-L3。然后使用ECL(罗氏E170电化学发光分析系统)检测处理前标本(总AFP)和处理后标本(AFP-L3), 通过计算可以获知检测标本中AFP-L3占总AFP的比率。凝集素亲和免疫电泳自显影法的主要操作为:将标本置于凝集素与凝胶混合制成的凝胶板中电泳分离, 而后将凝胶板旋转90度, 在添加含抗AFP、¹²⁵I-AFP的凝胶中进行2次电泳, 后将凝胶烘干, 覆盖X线胶片曝光, 冲洗成像。

肝功能指标(GGT、ALT、TBil、Alb)采用日立7600全自动生化分析仪检测。

四、统计学方法

应用SPSS 15.0软件进行统计分析。应用秩和检验、t检验、四格表χ ²检验、配对χ ²检验、行× 列表χ ²检验和Kappa一致性检验进行分析。P< 0.05表示差异有统计学意义。

结果

一、2种方法检测AFP-L3结果比较

凝集素亲和免疫电泳自显影法AFP-L3阳性检出率为50%, 凝集素捕获微量离心柱法阳性检出率为46%, 2种方法的阳性检出率差异无统计学意义(P> 0.05)。2种方法检测的Kappa系数为0.840(P=0.000), 两者符合率为92%[(22+24)/50]。见表1。

表1 2种方法检测AFP-L3结果比较

二、622例AFP阳性PLC患者的肝功能指标与AFP-L3的关系

在622例AFP阳性PLC患者中, AFP-L3阳性395例, AFP-L3阴性227例。AFP-L3阳性患者GGT、TBil水平高于AFP-L3阴性患者(P< 0.05), 而ALT和Alb水平两者间差异无统计学意义(P> 0.05), 见表2。

表2 622例AFP阳性PLC患者肝功能指标与AFP-L3的关系

三、646例PLC患者 AFP水平与AFP-L3阳性率的关系

646例PLC患者中, 24例AFP阴性(AFP为10~20 μ g/L)患者AFP-L3阳性4例, 阳性率为16.67%; 622例AFP阳性(AFP> 20 μ g/L)患者AFP-L3阳性395例, 阳性率为63.50%, 两者比较差异有统计学意义(χ ²=21.462, P=0.000)。将PLC患者的AFP-L3阳性率按AFP浓度进行分层。结果显示AFP-L3的总体阳性率为61.76%, 随着AFP浓度的升高, AFP-L3阳性率亦升高(χ ²=84.866, P=0.000)。见表3。

表3 AFP水平分层与AFP-L3阳性率的相关分析

四、AFP阳性良性肝脏疾病患者AFP-L3的检测结果

17例AFP阳性(AFP> 20 μ g/L)的良性肝脏疾病患者中AFP-L3阳性4例, 阳性率为23.53%, 显著低于AFP阳性PLC患者(χ ²=11.276, P=0.001)。

讨论

目前AFP-L3的检测方法主要有亲和免疫交叉电泳技术(显色方法有放射自显影法、酶标法、考马斯亮蓝法、金银染色法)和亲和印迹技术, 但这些方法都有技术要求较高、试剂昂贵、操作繁琐等缺点, 迄今没有在临床得到广泛推广使用。本研究将经典的凝集素亲和免疫电泳自显影法与国内新研制的凝集素捕获微量离心柱法进行了比较, 研究替代经典手工方法的可行性, 以期大量应用于临床检验。凝集素亲和免疫电泳自显影法以AFP-L3≥ 25%作为诊断临界值, 凝集素捕获微量离心柱法以AFP-L3≥ 10%作为诊断临界值, 结果显示2种方法的阳性检出率差异无统计学意义, 具有良好的一致性。由于凝集素捕获微量离心柱法操作简便省时, 更具有应用优势。

虽然AFP是目前公认的肝癌诊断标志物, 但对于临床PLC的诊断仍存在特异性不高等问题。据第15次日本全国PLC追踪调查发现, AFP阳性PLC患者有49%的病例AFP升高, 在21200 μ g/L范围内^[9]。若将500 μ g/L作为诊断上限, 很难对PLC和以病毒性肝硬化为主的良性肝脏疾病进行鉴别诊断。早在2002年, Yoshida等^[10]以AFP-L3> 15%作为是否正常的临界值, 发现AFP-L3与原发性肝细胞癌(HCC)分期和肿瘤大小有更高的相关性, 而AFP却不具备该相关性。Sterling等^[11]针对372例丙型肝炎病毒(HCV)感染患者进行了2年的随访研究发现, 高水平AFP-L3患者比高AFP患者发展为HCC的可能性更大, 研究同时还表明, AFP-L3诊断PLC的特异性在AFP 20200 ng/mL时为89.6%, 如此高的特异性提示在AFP 20200 ng/mL时AFP-L3对HCV患者有临床诊断价值。本研究以AFP-L3≥ 10%作为诊断临界值, 将AFP阳性PLC患者的AFP-L3阳性率按AFP浓度进行分层分析, 发现AFP-L3阳性率随AFP浓度升高而增加, AFP阳性PLC患者AFP-L3阳性率显著高于AFP阴性PLC患者和AFP阳性的良性肝脏疾病患者。因此对于AFP阴性PLC患者检测AFP-L3的临床意义不大, 但对于AFP升高的非PLC患者的鉴别诊断具有较重要的临床意义。本研究中入选的646例PLC患者AFP-L3的总体阳性率为61.76%。结合文献报道, 我们认为AFP-L3的检测对于PLC的辅助诊断、鉴别诊断有重要价值。

本研究同时发现, AFP-L3的阴、阳性与AFP阳性PLC患者的血清生化指标也有一定的相关性。AFP-L3阳性PLC患者GGT、TBil水平明显高于AFP-L3阴性PLC患者, 提示AFP-L3阳性PLC患者的预后将较差。

此外, AFP-L3在PLC疗效评估和预后判断中也有其独特的价值^{[12, 13]}。推断AFP-L3是预测肝癌预后的有用标志物, 但具体机制尚不十分清楚。

总之从本研究结果可以看出, 仅凭AFP诊断PLC容易造成漏诊及误诊, 单独使用AFP 或AFP-L3均有一定的局限性, 两者应联合使用, 互相补充, 以提高对PLC的诊断率。检测AFP-L3对于AFP阴性的PLC患者临床价值有限, 但对于AFP升高的非PLC患者, AFP-L3可作为排除PLC的依据之一辅助诊断。与AFP-L3的凝集素亲和免疫电泳自显影法比较, 凝集素捕获微量离心柱法操作更简便省时, 结果准确, 适合于临床检测应用。

The authors have declared that no competing interests exist.

参考文献

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2008

9.858

0.0

. 2008, 49(2):223-232 DOI:10.1016/j.jhep.2008.04.013

Prognostic value of pretreatment levels of tumor markers for hepatocellular carcinoma on survival after curative treatment of patients with HCC

Background/Aims We evaluated the prognostic value of the pretreatment elevation of tumor markers for hepatocellular carcinoma (HCC) in patients who underwent curative treatment. Methods We studied 801 patients who had been diagnosed as initial HCC and fulfilled the following criteria: maximum tumor size, ?3 cm; number of tumors, ?3; remnant liver function, Child-Pugh class A or B; treated by hepatectomy or locoregional thermal ablation (LTA); and alpha-fetoprotein (AFP), Lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3), and des-gamma carboxy prothrombin (DCP) were measured at diagnosis. We analyzed the effects of elevated tumor markers on patient survival in these 2 distinct groups with different types of treatment, i.e. hepatectomy and LTA. Results By multivariate analysis in 345 patients who underwent hepatectomy, no tumor marker significantly affected decreased survival rate. In the 456 patients who underwent LTA, the elevation of AFP-L3 ( p = 0.0171) and DCP ( p = 0.0004) significantly affected decreased survival rate; DCP elevation had the strongest effect on patient survival. Conclusions The prognostic value of pretreatment tumor marker elevation was different in patients who underwent the curative treatment according to the type of treatment. Pretreatment elevation of AFP-L3 and DCP had prognostic values only in patients treated with LTA.

... 引言虽然甲胎蛋白(AFP)是目前公认的原发性肝癌(PLC)的肿瘤标志物,广泛应用于肝癌的早期辅助诊断、疗效判断和预测复发中^[1],但因其敏感性和特异性均不够理想^[2~4],迫切需要有更好的指标 ...

2004

1.259

0.0

. 2004, 3(2):194-198

Changed clinical aspects of primary liver cancer in China during the past 30 years

Shanghai, China Author Affiliations: Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai 200032, China (Yang BH, Xia JL, Huang LW and Tang ZY); Tumor Hospital, Zhongshan University, Guangzhou 510000, China (Chen MS and Li JQ); Tumor Hospital, Guangxi Medical University, Nanning 530000, China (Liang AM and Mo QG); Xiehe Hospital, Fujian Medical University, Fuzhou 350000, China (Lu HS); Second Hospital, Chinese Medical University, Shenyang 110000, China (Dai CL); Huaxi Hospital, Sichuan University, Chengdu 610041, China (Yan LN); Hospital Affiliated to Nantong Medical University, Nantong 226000, China (Yu ZJ); Second Hospital, Jiangxi Medical University, Nanchang 330000, China (Rao RS); First Hospital Affiliated to Guangxi Medical University, Nanning 530000, China (Li LQ and Su ZX); People’s Hospital of Hainan Province, Haikou 570000, China (Fang ZW) Corresponding Author: Bing-Hui Yang, MD, Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai 200032, China (Tel: 86-21-64037250; Fax: 86-21-64037250; Email: bhyang@zshospital. net)

BACKGROUND: Primary liver cancer (PLC) is one of the most frequently seen tumors in China. Thirty years ago, patients with PLC were often detected at relatively late stage, with a palpable mass or marked clinical symptoms and poor prognosis. In the past 30 years, the diagnosis and treatment of PLC have been greatly improved with better prognosis. METHODS: In order to study the changes of PLC during the 30 years, the clinical data of 3250 patients with PLC from 10 medical institutions of China were collected, analyzed, and compared with those of 3254 PLC patients before the 30 years. RESULTS: In the 3250 patients aged 1-80 years, with an average age of 49.1 years, the male to female ratio (2.3∶1) was lower than that before the 30 years. 73.5% of the 3250 patients sought medical advice within 3 months after the onset of the disease in contrast to 63.8% before the 30 years. Compared with those patients before the 30 years the symptoms and signs were alleviated generally. The HBsAg positive rate was 81.0%, but the HCV-Ab positive rate was 13.2%. The AFP level in 75% of patients was elevated, but in the remaining 25% was normal. 1912 patients (58.8%) were confirmed pathologically. Among them 1755 patients (91.8%) had hepatocellular carcinoma. The overall resection rate was 46.3%. Those who had early, middle, late stage carcinoma accounted for 29.9%, 51.5%, and 18.6% respectively in contrast to 0.4%, 47.0%, and 52.6% reported before the 30 years. The 1-, 3-, 5-year survival rates of the patients were 66.1%, 39.7%, and 32.5% respectively, whereas 93.5%, 70.1%, and 59.1% for the early stage patients, and 65.3%, 30.5%, and 23.5% for the middle stage patients. The half and 1-year survival rates of the late stage patients were 52.5%, and 14.7%, respectively. CONCLUSION: Comparison with the clinical data before and after the 30 years show that PLC can be diagnosed early. More PLC patients tend to undergo resection while receiving a better conservative treatment, which ensures a prognosis.

2010

3.788

0.0

. 2010, 45(12):1272-1282 DOI:10.1007/s00535-010-0278-5

AFP, AFP-L3, DCP, and GP73 as markers for monitoring treatment response and recurrence and as surrogate markers of clinicopathological variables of HCC

1.Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan 2.Department of Biostatistics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan 3.Department of Clinical Laboratory Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan 4.INOVA Diagnostics, Inc., San Diego, CA USA 5.Department of Hepatobiliary-Pancreatic Surgery, Juntendo School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421 Japan

Background Alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), des-γ-carboxy prothrombin (DCP), and Golgi protein-73 (GP73) have been used or proposed as tumor markers for hepatocellular carcinoma (HCC).

2000

0.0

2007

0.0

... 研究发现肝病伴随多种蛋白异常糖基化^[5],在不同生理病理状态下产生不同的糖链结构,且具有肿瘤特异性 ...

2010

0.0

. 2010, 55(10):2744-2755 DOI:10.1007/s10620-010-1184-7

Serum markers of hepatocellular carcinoma

1.Department of Biomedical Science, University of Catania, Via Androne 83, 95124 Catania, Italy 2.Senescence, Urological, and Neurological Sciences, University of Catania, Via Messina 829, 95126, Catania, Italy 3.Department of Medical Oncology, National Cancer Institute, Via Franco Gallini 2, 33081 Aviano (PN), Italy 4.Section of General Surgery and Oncology, Department of General Surgery, University Medical School of Catania, Ospedale Vittorio Emanuele Via Plebiscito 628, 95100 Catania, Italy

Background The hepatocellular carcinoma is one of the most common malignant tumors and carries a poor survival rate. The management of patients at risk for developing HCC remains intricate.

... 甲胎蛋白异质体3(AFP-L3)与LCA有结合活性,主要由肿瘤细胞产生^[6] ...

2008

2.719

0.0

... 5%^[7] ...

2007

0.752

0.0

. 2007, 70(8):310-317 DOI:10.1016/S1726-4901(08)70011-X

AFP-L3 in chronic liver diseases with persistent elevation of alpha-fetoprotein

Background Alpha-fetoprotein (AFP) is an important marker for hepatocellular carcinoma (HCC). However, persistent elevation of AFP is found in patients with chronic liver diseases. The value of AFP-L3, which is more specific than AFP, was examined in such patients. Methods We enrolled patients without image-detectable tumor, but with transient AFP value > 900 ng/mL (group A) or with persistent AFP value > 50 ng/mL for longer than 6 months (group B). Forty-one patients with HCC and AFP value > 50 ng/mL were included as the HCC control group (group C). AFP-L3 measurement was done by lectin-affinity electrophoresis coupled with antibody-affinity blotting. The study patients were followed with AFP, liver biochemistry and abdominal ultrasound at 3- to 6-month intervals. Additional studies were done when a tumor was suspected. Results One of 17 patients in group A and 13 of 39 patients in group B developed HCC within 2 years. When the cutoff value of AFP-L3 ratio was 15%, both the sensitivity and specificity were 71% for prediction of HCC during the next 2 years in all patients. Ninety percent of tumors larger than 5 cm had AFP-L3 > 15%, compared with only 60% for tumors smaller than 2 cm. Three patients in group A had AFP-L3 ratio > 17.5%. One patient developed HCC 10 months later; the other 2 patients were associated with hepatic failure. Conclusion AFP-L3 provides a clue in HCC detection in patients with persistent elevation of AFP. However, AFP-L3 could be highly elevated in severe hepatitis.

... AFP-L3已于2005年被美国食品与药品监督管理局(FDA)批准为PLC的肿瘤标志物^[8] ...

2005

0.0

... g/L范围内^[9] ...

2002

2.657

0.0

... 早在2002年,Yoshida等^[10]以AFP-L3#cod#x0003E ...

2007

7.553

0.0

. 2007, 102(10):2196-2205

Clinical Utility of AFP-L3|[percnt]| Measurement in North American Patients with HCV-Related Cirrhosis

The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastroenterological disorders seen most often in patients. Published with practicing clinicians in mind, the journal aims to be easily accessible, organizing its content by topic, both online and in print. www.amjgastro.com, *2007 Journal Citation Report (Thomson Reuters, 2008)

... Sterling等^[11]针对372例丙型肝炎病毒(HCV)感染患者进行了2年的随访研究发现,高水平AFP-L3患者比高AFP患者发展为HCC的可能性更大,研究同时还表明,AFP-L3诊断PLC的特异性在AFP 20200 ng/mL时为89 ...

2007

0.0

Dig Dis Sci. 2007, 52(3):776-782

Clinical Evaluation of Lens Culinaris Agglutinin-Reactive α-Fetoprotein and Des-γ-Carboxy Prothrombin in Histologically Proven Hepatocellular Carcinoma in the United States

Brian I. Carr (1) , Futoshi Kanke (2) , Margaret Wise (3) , Shinji Satomura (2)

1. Liver Cancer Center, Starzl Transplantation Institute, University of Pittsburgh Medical Center, E1552 BST, 200 Lothrop Street, Pittsburgh, Pennsylvania, 15213, USA 2. Diagnostics Division, Wako Pure Chemical Industries, Ltd., Osaka, Japan 3. Diagnostics Division, Wako Chemicals USA, Inc., Richmond, Virginia, USA

There is no established clinical role for the lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3%) and des-γ-carboxy prothrombin (DCP) in the management of the U.S. hepatocellular carcinoma (HCC) patient population. In order to clarify the clinical usefulness and characteristics of AFP-L3% and DCP, a prospective study was performed on United States patients having histologically proven hepatocellular carcinoma. Ninety-nine histologically proven HCC patients, who were diagnosed with unresectable cancer between July 1999 and March 2001 at the Liver Cancer Center of the University of Pittsburgh Medical Center, were included for analysis. The sensitivity of AFP-L3%, DCP, and AFP was 61.6%, 72.7%, and 67.7%, respectively. The highest sensitivity, 85.9%, was obtained in the combination of three markers. Statistically significant differences were observed for portal vein invasion in AFP-L3% and AFP levels ( P =0.0059 and P =0.0360, respectively). DCP was significantly associated with metastasis ( P =0.0368). There were significant associations between AFP-L3% and AFP results and patient survival ( P =0.0150 and P= 0.0020, respectively). AFP-L3%, platelet count,and albumin showed a significant difference with respect to outcomes on Cox’s proportional hazard model ( P =0.0059, P= 0.0073, and P= 0.0265, respectively). The combination of AFP-L3%, DCP, and AFP was determined to be superior for detection of HCC compared with each marker alone or to other combinations. AFP-L3% was significantly related to portal vein invasion and patient outcomes and appears to be a useful prognostic marker for HCC.

... 此外,AFP-L3在PLC疗效评估和预后判断中也有其独特的价值^[12,13] ...

2005

3.87

0.0

. 2005, 25(4):848-853

Relationship between Lens culinaris agglutinin-reactive α-fetoprotein and pathologic features of hepatocellular carcinoma

Toshifumi Tada 1 ,Takashi Kumada 1 ,Hidenori Toyoda 1 ,Seiki Kiriyama 1 ,Yasuhiro Sone 1 ,Makoto Tanikawa 1 ,Yasuhiro Hisanaga 1 ,Shusuke Kitabatake 1 ,Teiji Kuzuya 1 ,Koji Nonogaki 1 ,Junichi Shimizu 1 ,Akihiro Yamaguchi 2 ,Masatoshi Isogai 2 ,Yuji Kaneoka 2 ,Junji Washizu 2 andShinji Satomura 3

1 Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan, 2 Department of Surgery, Ogaki Municipal Hospital, Ogaki, Japan, 3 Diagnostic Division, Wako Pure Chemical Industries Ltd., Osaka, Japan * Takashi Kumada, MD, Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu 503-8502, Japan. Tel: +81-584-81-3341 Fax: +81-584-75-5715 e-mail: tkumada@he.mirai.ne.jp

> Abstract: Aim: We investigated pathological features of Lens culinaris agglutinin-reactive α-fetoprotein (AFP-L3)-positive hepatocellular carcinoma (HCC) in order to seek a pathological basis of poor prognosis of HCC patients with elevated AFP-L3.

... 此外,AFP-L3在PLC疗效评估和预后判断中也有其独特的价值^[12,13] ...