Comparison of plasma Epstein-Barr virus (EBV) DNA levels and serum EBV immunoglobulin A/virus capsid antigen antibody titers in patients with nasopharyngeal carcinoma

Comparison of plasma Epstein-Barr virus (EBV) DNA levels and serum EBV immunoglobulin A/virus capsid antigen antibody titers in patients with nasopharyngeal carcinoma
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DOI:
10.1002/cncr.20099
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发表时间:
2004-03-15
期刊:
影响因子:
6.2
通讯作者:
Zeng, YX
Zeng, YX
中科院分区:
医学1区
文献类型:
--
作者:
Shao, JY;Li, YH;Zeng, YX

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背景EB病毒(Epstein-Barr virus,EBV)免疫球蛋白A/病毒衣壳抗原(伊加/VCA)和早期抗原(伊加/EA)抗体的血清学检测已广泛应用于鼻咽癌(NPC)的筛查。近年来发现血浆EBV DNA浓度可作为鼻咽癌分期和预后的一个指标。为探讨鼻咽癌患者血浆EB病毒DNA水平与血清伊加/VCA水平之间是否存在相关性,对鼻咽癌患者和正常对照组进行了检测。采用实时聚合酶链反应定量分析血浆EB病毒DNA浓度,采用酶联免疫吸附法测定原发性NPC患者的EB病毒VCA/伊加(n = 120例患者),局部复发性NPC(n = 8例患者)和远处转移性NPC(n = 21例)在76例NPC患者完成放疗后,在60例NPC患者的临床缓解,在38例非NPC肿瘤患者,并在47个对照个体。原发性、局部复发性和远处转移性NPC患者的中位血浆EBV DNA水平分别为6200拷贝/mL、9200拷贝/ mL和2050拷贝/mL,但在临床缓解性NPC患者、完成放疗的患者、非NPC肿瘤患者和对照组中降至0拷贝/mL。与此相反,EB病毒VCA/伊加滴度和检出率在所有NPC组中仍然很高。血清VCA/伊加滴度大于或等于1:640(中位数,83,450拷贝/mL)的患者血浆EBV DNA水平显著高于滴度小于或等于1:320(中位数,17,200拷贝/mL)的患者。晚期TNM分期(III期和IV期;中位数,8530拷贝/mL)和T分类(T3和T4肿瘤;中位数,8530拷贝/mL)的NPC患者的血浆EBV DNA水平显著高于早期TNM分期(I期和II期;中位数,930拷贝/mL)和T分类(T1和T2肿瘤;中位数,3700拷贝)的患者。晚期TNM分期NPC患者的平均VCA/伊加滴度(1:424)明显高于早期TNM分期NPC患者(1:246),但伊加/VCA滴度与NPC的T或N分类无关。结论。结果提示,血浆EBVDNA检测是一种较血清伊加/VCA滴度更敏感、特异的鼻咽癌诊断和监测指标。这些结果为血浆EBV DNA检测用于鼻咽癌的早期诊断、分期以及监测肿瘤的复发和转移提供了有力的证据。(C)2004年美国癌症协会。
BACKGROUND. Serologic measurement of antibodies to Epstein-Barr virus (EBV) immunoglobulin A/viral capsid antigen (IgA/VCA) and early antigen (IgA/EA) has been used widely to screen for nasopharyngeal carcinoma (NPC) in China. Recently, it was found that plasma EBV DNA concentration is an indicator for the staging and prognosis of patients with NPC. To determine whether there is a correlation between plasma EBV DNA levels and serum levels of IgA/VCA, the authors measured both in patients with NPC and in a control group.METHODS. Real-time polymerase chain reaction was used for quantitative analysis of plasma EBV DNA concentration, and enzyme-linked immunoadsorbent assay was used to measure EBV VCA/IgA in patients with primary NPC (n = 120 patients), locally recurrent NPC (n = 8 patients), and distant metastatic NPC (n = 21 patients) among 76 patients with NPC after the completion of radiotherapy, in 60 patients with NPC in clinical remission, in 38 patients with non-NPC tumors, and in 47 control individuals.RESULTS. The median plasma EBV DNA levels were 6200 copies/mL, 9200 copies/ mL, and 2050 copies/mL in patients with primary, locally recurrent, and distant metastatic NPC, respectively, but declined to 0 copies/mL in patients with clinically remissive NPC, in patients who completed radiotherapy, in patients with non-NPC tumors, and in the control group. In contrast, EBV VCA/IgA titers and detection rates remained high in all NPC groups. Plasma EBV DNA levels were significantly higher in patients who had serum VCA/IgA titers greater than or equal to 1:640 (median, 83,450 copies/mL) compared with the levels in patients who had titers less than or equal to 1:320 (median, 17,200 copies/mL). Patients with NPC who had advanced TNM stage (Stages III and IV; median, 8530 copies/mL) and T classification (T3 and T4 tumors; median, 8530 copies/mL) had significantly higher plasma EBV DNA levels compared with patients who had early TNM stage (Stages I and II; median, 930 copies/mL) and T classification (T1 and T2 tumors; median, 3700 copies). Patients who had advanced TNM stage NPC had significantly higher mean VCA/IgA titers (1:424) compared with patients who had early TNM stage NPC (1:246), but there was no correlation between IgA/VCA titer and T or N classification of NPC.CONCLUSIONS. The results suggest that plasma EBV DNA detection is a more sensitive and specific marker than the serum IgA/VCA titer for the diagnosis and monitoring of patients with NPC. These findings provide convincing evidence for the use of plasma EBV DNA measurements for the early diagnosis and staging of NPC as well as for monitoring recurrence and metastasis of this tumor. (C) 2004 American Cancer Society.