Shao Jian-Yong, Li Yu-Hong, Gao Hong-Yi, Wu Qiu-Liang, Cui Nian-Ji, Zhang Li, Cheng Gang, Hu Li-Fu, Ernberg Ingemar, Zeng Yi-Xin
Cancer Center, Sun Yat-Sen University, Guangzhou, People's Republic of China.
Cancer. 2004 Mar 15;100(6):1162-70. doi: 10.1002/cncr.20099.
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.
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.
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 > or = 1:640 (median, 83,450 copies/mL) compared with the levels in patients who had titers < or = 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.
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.
在中国，血清学检测爱泼斯坦-巴尔病毒（EBV）免疫球蛋白A/病毒衣壳抗原（IgA/VCA）和早期抗原（IgA/EA）抗体已被广泛用于鼻咽癌（NPC）筛查。最近发现，血浆EBV DNA浓度是NPC患者分期和预后的一个指标。为确定血浆EBV DNA水平与血清IgA/VCA水平之间是否存在相关性，作者对NPC患者和对照组进行了这两项指标的检测。
采用实时聚合酶链反应对血浆EBV DNA浓度进行定量分析，采用酶联免疫吸附测定法检测76例放疗后NPC患者中的原发性NPC患者（n = 120例）、局部复发性NPC患者（n = 8例）和远处转移性NPC患者（n = 21例）、60例临床缓解期NPC患者、38例非NPC肿瘤患者及47例对照个体的EBV VCA/IgA。
原发性、局部复发性和远处转移性NPC患者的血浆EBV DNA水平中位数分别为6200拷贝/mL、9200拷贝/mL和2050拷贝/mL，但临床缓解期NPC患者、完成放疗的患者、非NPC肿瘤患者及对照组患者的血浆EBV DNA水平降至0拷贝/mL。相比之下，所有NPC组的EBV VCA/IgA滴度和检出率仍较高。血清VCA/IgA滴度≥1:640的患者血浆EBV DNA水平（中位数，83450拷贝/mL）显著高于滴度≤1:320的患者（中位数，17200拷贝/mL）。TNM分期为晚期（III期和IV期；中位数，8530拷贝/mL）和T分级为T3和T4肿瘤（中位数，8530拷贝/mL）的NPC患者血浆EBV DNA水平显著高于TNM分期为早期（I期和II期；中位数，930拷贝/mL）和T分级为T1和T2肿瘤（中位数，3700拷贝）的患者。TNM分期为晚期的NPC患者的平均VCA/IgA滴度（1:424）显著高于TNM分期为早期的NPC患者（1:246），但IgA/VCA滴度与NPC的T或N分级之间无相关性。
结果表明，对于NPC患者的诊断和监测，血浆EBV DNA检测是比血清IgA/VCA滴度更敏感、更特异的标志物。这些发现为血浆EBV DNA检测用于NPC的早期诊断和分期以及监测该肿瘤的复发和转移提供了令人信服的证据。
