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Title: Comparison of the prognostic impact of serum anti-EBV antibody and plasma EBV DNA assays in nasopharyngeal carcinoma

Abstract

Purpose: Nasopharyngeal carcinoma (NPC) has been proven as an Epstein-Barr virus (EBV)-associated cancer. Serum anti-EBV antibodies and plasma EBV DNA have been investigated as surrogate markers for NPC. A comparison of the prognostic impacts of both assays has never been reported. Methods and Materials: Paired serum and plasma samples from 114 previously untreated NPC patients were collected and subjected to an immunofluorescence assay for immunoglobulin (Ig)A and IgG antibodies against the viral capsid antigen (VCA) and a real-time quantitative polymerase chain reaction assay for EBV DNA measurement. The effects of both assays on patient prognosis were thoroughly investigated. Results: Relapsed patients had significantly higher pretreatment EBV DNA concentration than patients without relapse (p 0.0006). No associations of VCA-IgA (p = 0.9669) or VCA-IgG (p = 0.6125) were observed between patients with and without relapse. The 4-year overall survival (60.3% vs. 93.1%, p < 0.0001) and relapse-free survival rates (54.4% vs. 77.9%, p = 0.0009) were significantly lower in patients with higher pretreatment EBV DNA load than in those with lower EBV DNA load. Patients with persistently detectable EBV DNA after treatment had significantly worse 4-year overall (30.8% vs. 84.6%, p < 0.0001) and relapse-free survival rates (15.4% vs. 74.0%, pmore » < 0.0001) than those with undetectable EBV DNA. The VCA-IgA and VCA-IgG titer could not predict survivals (all p > 0.1). Cox multivariate analyses also showed the same results. Conclusion: Plasma EBV DNA is superior to serum EBV VCA antibodies in prognostic predictions for NPC.« less

Authors:
 [1];  [2];  [3];  [4];  [5];  [6];  [5];  [7];  [8]
  1. Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China)
  2. (China)
  3. Section of Basic Medicine, Department of Nursing, Hung Kuang University, Taichung (China)
  4. Department of Public Health, China Medical University, Taichung (China)
  5. Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung (China)
  6. Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung (China)
  7. Department of Pathology, National Cheng Kung University Hospital, Tainan (China)
  8. Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China) and Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung (China) and Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan (China). E-mail: jclin@vghtc.gov.tw
Publication Date:
OSTI Identifier:
20850305
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 67; Journal Issue: 1; Other Information: DOI: 10.1016/j.ijrobp.2006.07.012; PII: S0360-3016(06)01172-2; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANTIBODIES; ANTIGENS; CARCINOMAS; DNA; IMMUNOGLOBULINS; MULTIVARIATE ANALYSIS; ONCOGENIC VIRUSES; PATIENTS; POLYMERASE CHAIN REACTION

Citation Formats

Twu, C.-W., Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Wang, W.-Y., Liang, W.-M., Jan, J.-S., Jiang, R.-S., Chao, Jeffrey, Jin, Y.-T., and Lin, J.-C. Comparison of the prognostic impact of serum anti-EBV antibody and plasma EBV DNA assays in nasopharyngeal carcinoma. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.07.012.
Twu, C.-W., Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Wang, W.-Y., Liang, W.-M., Jan, J.-S., Jiang, R.-S., Chao, Jeffrey, Jin, Y.-T., & Lin, J.-C. Comparison of the prognostic impact of serum anti-EBV antibody and plasma EBV DNA assays in nasopharyngeal carcinoma. United States. doi:10.1016/j.ijrobp.2006.07.012.
Twu, C.-W., Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Wang, W.-Y., Liang, W.-M., Jan, J.-S., Jiang, R.-S., Chao, Jeffrey, Jin, Y.-T., and Lin, J.-C. Mon . "Comparison of the prognostic impact of serum anti-EBV antibody and plasma EBV DNA assays in nasopharyngeal carcinoma". United States. doi:10.1016/j.ijrobp.2006.07.012.
@article{osti_20850305,
title = {Comparison of the prognostic impact of serum anti-EBV antibody and plasma EBV DNA assays in nasopharyngeal carcinoma},
author = {Twu, C.-W. and Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung and Wang, W.-Y. and Liang, W.-M. and Jan, J.-S. and Jiang, R.-S. and Chao, Jeffrey and Jin, Y.-T. and Lin, J.-C.},
abstractNote = {Purpose: Nasopharyngeal carcinoma (NPC) has been proven as an Epstein-Barr virus (EBV)-associated cancer. Serum anti-EBV antibodies and plasma EBV DNA have been investigated as surrogate markers for NPC. A comparison of the prognostic impacts of both assays has never been reported. Methods and Materials: Paired serum and plasma samples from 114 previously untreated NPC patients were collected and subjected to an immunofluorescence assay for immunoglobulin (Ig)A and IgG antibodies against the viral capsid antigen (VCA) and a real-time quantitative polymerase chain reaction assay for EBV DNA measurement. The effects of both assays on patient prognosis were thoroughly investigated. Results: Relapsed patients had significantly higher pretreatment EBV DNA concentration than patients without relapse (p 0.0006). No associations of VCA-IgA (p = 0.9669) or VCA-IgG (p = 0.6125) were observed between patients with and without relapse. The 4-year overall survival (60.3% vs. 93.1%, p < 0.0001) and relapse-free survival rates (54.4% vs. 77.9%, p = 0.0009) were significantly lower in patients with higher pretreatment EBV DNA load than in those with lower EBV DNA load. Patients with persistently detectable EBV DNA after treatment had significantly worse 4-year overall (30.8% vs. 84.6%, p < 0.0001) and relapse-free survival rates (15.4% vs. 74.0%, p < 0.0001) than those with undetectable EBV DNA. The VCA-IgA and VCA-IgG titer could not predict survivals (all p > 0.1). Cox multivariate analyses also showed the same results. Conclusion: Plasma EBV DNA is superior to serum EBV VCA antibodies in prognostic predictions for NPC.},
doi = {10.1016/j.ijrobp.2006.07.012},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 1,
volume = 67,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}
  • Raji cells, an EBV genome carrying and nonproducer cell line, treated with tetradecanoyl-phorbol-13-acetate (TPA) and n-butyrate could induce a special DNA polymerase which has properties that are similar to the EBV-DP induced by TPA in P/sub 3/HR-I cells, an EBV producer cell line. Since EBV was found to have a strong association with NPC, and antibodies against EBV proteins or enzymes were found in high levels in sera from these patients, the possible presence of serum antibody against EBV-DP was examined. The serum titer of antibody to EBV-DP was found to have 190 +/- 84 units/ml serum (mean +/- S.D.)more » in 48 sera from patients with NPC. The titer in 52 healthy donors was 31.4 +/- 28 unit/ml serum (p < 0.01). The antibody was found to be associated with the IgG but not the IgA fraction. The antibody titers against EBV-DP were not correlated with the titer against EBV-DNase or VCA-IgA. Whether the antibody observed is against an EBV-DP core protein or its stimulating protein, as demonstrated by this laboratory previously, is still being investigated. This study demonstrated the high frequency and high titer of antibody against EBV-DP in serum from patients with NPC, and suggested the potential of utilizing this antibody titer to compliment other methods for the early diagnosis or prognosis of NPC.« less
  • A one-step procedure which uses enzymes in a crude extract of herpes simplex virus (HSV) type 1-infected cells to synthesize 5-(125I)iodo-2'-deoxyuridine triphosphate (( 125I)dUTP) from (125I)dU is described. The design of a one-step procedure for the purification of the product is also presented. The recovery of (125I)dUTP from (125I)dU varied between 50 and 75%, the radiochemical purity of the product was greater than 90%, and both synthesis and purification were completed within 8 h. The sensitivity and specificity of (125I)dUTP as a substrate for both DNA-dependent DNA polymerase (DNAp) and RNA-dependent DNA polymerase (reverse transcriptase, RT) were evaluated and comparedmore » to those of (3H)dTTP for the following specimens: purified cloned Klenow fragment, crude extracts of HeLa-, BHK-, and HSV-2-infected BHK cells, purified avian myeloblastosis virus RT, and purified cloned human immunodeficiency virus (HIV) RT. The (125I)dUTP was accepted as a substrate equally as well (3H)dTTP by all of the specimens at all of the concentrations tested. When the same amount of radiolabel was used, (125I)dUTP gave a sensitivity 10- to 25-fold higher than that of (3H)dTTP. The gain in sensitivity was due to the higher specific activity and a higher counting efficiency of the 125I-label compound. The use of (125I)dUTP also offered technical advantages over alternative substrates available, such as product separation without acid precipitation and exclusion of the need for scintillation cocktails. The half-life of the nucleic also gives a reasonable shelf-life for use in routine assays. Activity of less than 0.3 pg of HIV RT could be detected when the new substrate was used, and this made it possible to quantitate HIV RT antibodies (abs) in diluted serum samples without purifying the immunoglobulin.« less
  • Purpose: To evaluate the long-term prognostic impact of plasma Epstein-Barr virus (EBV) DNA concentration measured by real-time quantitative polymerase chain reaction (RTQ-PCR) in nasopharyngeal carcinoma (NPC) patients receiving concurrent chemoradiotherapy (CCRT). Methods and Materials: Epstein-Barr virus DNA was retrospectively measured from stock plasma of 152 biopsy-proven NPC patients with Stage II-IV (M0) disease with a RTQ-PCR using the minor groove binder-probe. All patients received CCRT with a median follow-up of 78 months. We divided patients into three subgroups: (1) low pretreatment EBV DNA (<1,500 copies/mL) and undetectable posttreatment EBV DNA (pre-L/post-U) (2) high pretreatment EBV DNA ({>=}1,500 copies/mL) and undetectablemore » posttreatment EBV DNA (pre-H/post-U), and (3) low or high pretreatment EBV DNA and detectable posttreatment EBV DNA (pre-L or H/post-D) for prognostic analyses. Results: Epstein-Barr virus DNA (median concentration, 573 copies/mL; interquartile range, 197-3,074) was detected in the pretreatment plasma of 94.1% (143/152) of patients. After treatment, plasma EBV DNA decreased or remained 0 for all patients and was detectable in 31 patients (20.4%) with a median concentration 0 copy/mL (interquartile range, 0-0). The 5-year overall survival rates of the pre-L/post-U, pre-H/post-U, and pre-L or H/post-D subgroups were 87.2%, 71.0%, and 38.7%, respectively (p < 0.0001). The relapse-free survival showed similar results with corresponding rates of 85.6%, 75.9%, and 26.9%, respectively (p < 0.0001). Multivariate Cox analysis confirmed the superior effects of plasma EBV DNA compared to other clinical parameters in prognosis prediction. Conclusion: Plasma EBV DNA is the most valuable prognostic factor for NPC. More chemotherapy should be considered for patients with persistently detectable EBV DNA after CCRT.« less
  • Purpose: To explore the prognostic value of the plasma load of Epstein-Barr viral (EBV) DNA and the tumor response to neoadjuvant chemotherapy (NACT) in advanced-stage nasopharyngeal carcinoma (NPC). Patients and Methods: In all, 185 consecutive patients with stage III to IVb NPC treated with NACT followed by concurrent chemoradiation therapy (CCRT) were prospectively enrolled. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included locoregional relapse–free survival (LRFS) and distant metastasis–free survival (DMFS). Results: EBV DNA was detected in 165 (89%) patients before treatment but was undetectable in 127 (69%) patients after NACT. Detectable EBV DNA levels aftermore » NACT were correlated with poor prognosis (3-year PFS 71.8% vs 85.2%, P=.008 and 3-year DMFS 82.5% vs 92.3%, P=.013). An unsatisfactory tumor response (stable disease or disease progression) after NACT was also correlated with poor clinical outcome (3-year PFS 71.1% vs 85.9%, P=.005 and 3-year LRFS 82.7% vs 93.5%, P=.012). Multivariate analysis showed that the EBV DNA level after NACT (hazard ratio [HR] 2.31, 95% CI 1.18-4.54, P=.015) and the tumor response to NACT (HR 2.84, 95% CI 1.42-5.67, P=.003) were both significant prognostic factors for PFS. Multivariate analysis also showed that EBV DNA after NACT was the only significant predictor of DMFS (HR 2.99, 95% CI 1.25-7.15, P=.014) and that tumor response to NACT was the only significant predictor of LRFS (HR 3.31, 95% CI 1.21-9.07, P=.020). Conclusion: Detectable EBV DNA levels and an unsatisfactory tumor response (stable disease or disease progression) after NACT serve as predictors of poor prognosis for patients with advanced-stage NPC. These findings will facilitate further risk stratification, early treatment modification, or both before CCRT.« less