Detection of Epstein-Barr virus (EBV) genomes in the serum of patients with EBV-associated Hodgkin's disease

Gallagher, Alice; Armstrong, Alona; MacKenzie, Jane; Shield, Lesley; Khan, Gulfaraz; Lake, Annette; Proctor, Stephen J.; Taylor, Penny; Clements, G. B.; Jarrett, Ruth F.

doi:10.1002/(sici)1097-0215(19990820)84:4<442::aid-ijc20>3.0.co;2-j

Cited by 151 publications

(109 citation statements)

References 21 publications

(19 reference statements)

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“…2,3 This approach has been used recently in patients with EBV-associated Hodgkin disease, showing promising results. 12,13 With regard to patients with NPC, a few studies have been completed recently, a number of which have reflected diverse results using different PCR-based approaches. Researchers from Hong Kong 5 reported an extremely high detection rate of cell free EBV genomes in patients with primary NPC (55 of 57 patients; 96%) using a real-time, quantitative, PCR-based approach.…”

Section: Discussionmentioning

confidence: 99%

“…15 The source of cell free EBV DNA in circulation of patients with EBV-harboring malignancy remains somewhat controversial. Intact EBV particles 10,16,17 or free EBV DNA molecules released through the process of tumor death 9,12,18 both may exist in the circulation of patients with active disease. Conversely, in contrast to previous reports 9,10 suggesting that no cell free EBV could be detected in serum samples from patients with NPC in clinical remission, we were able to detect cell free EBV DNA in 36.5% of serum samples derived from patients with NPC who were in remission, and occasional (7.1%) high EBV DNA copy numbers (as indicated by positive results from 35-cycle PCR) were noted.…”

Section: Discussionmentioning

confidence: 99%

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Detection of cell free Epstein–Barr virus DNA in sera from patients with nasopharyngeal carcinoma

Hsiao

Jin

Tsai

2002

Cancer

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BACKGROUNDThe detection of tumor‐derived DNA within the circulation of patients with malignant disease using polymerase chain reaction (PCR)‐based strategies has opened a new avenue for the diagnosis and monitoring of these patients. Because of the universal association of Epstein–Barr virus (EBV) with the nonsquamous type of nasopharyngeal carcinoma (NPC; World Health Organization types II and III), the detection of cell free EBV DNA in sera from patients with NPC may be a valuable tool for monitoring the progress of tumors or to provide advanced warning of tumor recurrence.METHODSSerum samples were obtained from different patients, and cell free EBV DNA was detected with a conventional PCR approach. A total of 134 patients were sampled, including 36 patients with primary NPC, 28 control patients, 18 patients suffering from locoregional recurrence, 7 patients with distant metastasis, and 45 patients with NPC in clinical remission. A conventional PCR approach employing standard 35‐cycle and 50‐cycle reactions was used to detect cell free EBV genomes. Results from the two PCR cycles were compared to provide a semiquantitative picture of the relative quantity of EBV genome in each serum sample.RESULTSThe EBV DNA detection rates, i.e., the rates of positive detection, for 35‐cycle and 50‐cycle PCR analyses, respectively, were 38.9% and 75% for patients with primary NPC, 3.5% and 10.7% for control patients, 27.8% and 88.9% for patients with locoregional disease recurrence, 71.4% and 100% for patients with distant metastasis, and 7.1% and 36.5% for patients with disease in clinical remission. The rates of positive detection among patients with active disease all appeared to be significantly greater compared with the rates among patients with disease in clinical remission. Longitudinal data for six patients with recurrent tumors revealed a close correlation between the relative quantity of circulating cell free EBV genomes and the disease course of these patients. The sensitivity, specificity, positive predictive value, and negative predictive value of the 50‐cycle PCR analysis for detecting recurrent disease were 92%, 63.5%, 42.6%, and 96.4%, respectively.CONCLUSIONSThis study demonstrated that, by using a 50‐cycle PCR‐based approach, high sensitivity and high negative predictive value for detecting recurrent disease can be obtained from the detection of the cell free EBV genome in sera from patients with NPC. The 50‐cycle PCR analysis, therefore, may provide a simple, clinically useful adjuvant method for monitoring patients with NPC. Cancer 2002;94:723–9. © 2002 American Cancer Society.DOI 10.1002/cncr.10251

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Detection of cell free Epstein–Barr virus DNA in sera from patients with nasopharyngeal carcinoma

Hsiao

Jin

Tsai

2002

Cancer

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“…Real-time PCR is a rapid and reproducible method for quantifying DNA that was first introduced for EBV in 1999 [31,[42][43][44]. Real-time PCR measures the accumulation of PCR products with either a fluorogenic probe or SYBR green I dye, coupled with real-time laser scanning.…”

Section: Technical Aspects In Measuring Ebv Load In Peripheral Bloodmentioning

confidence: 99%

“…Indeed, cell-free EBV DNA is detected in the serum of most patients with EBV-associated Hodgkin's lymphoma [42]. EBV load in the serum or plasma is correlated with therapeutic responses [86], and EBV positivity in post-treatment samples indicates a poor prognosis [42]. Thus, serum and plasma are optimal samples to monitor Hodgkin's lymphoma (Table 3).…”

Section: Aids-related Lymphomamentioning

confidence: 99%

Measuring Epstein–Barr virus (EBV) load: the significance and application for each EBV‐associated disease

Kimura

Ito

Suzuki

et al. 2008

Reviews in Medical Virology

139

142

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Because Epstein-Barr virus (EBV) is ubiquitous and persists latently in lymphocytes, simply detecting EBV is insufficient to diagnose EBV-associated diseases. Therefore, measuring the EBV load is necessary to diagnose EBVassociated diseases and to explore EBV pathogenesis. Due to the diverse biology of EBV, the significance of measuring EBV DNA and the optimal type of specimen differ among EBV-associated diseases. Recent advances in molecular technology have enabled the EBV genome to be quantitated rapidly and accurately. Real-time polymerase chain reaction (PCR) is a rapid and reliable method to quantify DNA and is widely used not only as a diagnostic tool, but also as a management tool for EBV-associated diseases. However, each laboratory currently measures EBV load with its own ''homebrew'' system, and there is no consensus on sample type, sample preparation protocol, or assay units. The EBV real-time PCR assay system must be standardised for large-scale studies and international comparisons.

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“…57 More research is needed on this and other EBV-related diseases to define more fully the clinical utility of EBV viral load assays.…”

Section: Ebv Viral Load Measurement By Quantitative Dna Amplificationmentioning

confidence: 99%

Molecular Diagnosis of Epstein-Barr Virus-Related Diseases

Gulley

2001

The Journal of Molecular Diagnostics

294

237

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Epstein-Barr virus (EBV) is the causative agent of in-fectious mononucleosis, and it may also be found in a wide variety of benign and malignant lesions including oral hairy leukoplakia, inflammatory pseudotumor, Hodgkin's disease, non-Hodgkin's lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. Molecular testing is increasingly important in the diagnosis and monitoring of patients affected by these diseases. In biopsy tissues, molecular detection of EBV-encoded RNA transcripts by in situ hybridization remains the gold standard for proving that a histopathological lesion is EBV-related. EBV-encoded RNA hybridization and EBV LMP1 immunostains are used routinely to detect latent EBV in tissues affected by posttransplant lymphoproliferative disorder (PTLD) or in enlarged nodes from patients with infectious mononucleosis. Traditional serology is the best test for evaluating acute versus remote infection in healthy individuals. High serological titers serve as a tumor marker for some EBV-related malignancies, but titers are not a dependable tumor marker in immunocompromised hosts. EBV viral load testing by quantitative DNA amplification of blood samples is a promising new laboratory test that has proven useful for early diagnosis and monitoring patients with PTLD. Recent studies suggest a role for EBV viral load testing in nasopharyngeal carcinoma, Hodgkin's disease, and AIDS patients with brain lymphoma. Further research is needed to define more fully the clinical utility of viral load tests in the full spectrum of EBV-associated diseases. Gene expression profiling is on the horizon as a means to improve subclassification of EBV-related diseases and to predict response to therapy. In subsequent decades, EBV has been linked to a wide variety of benign and neoplastic diseases. Nasopharyngeal carcinomas and posttransplant lymphoproliferative disorders are nearly always EBV-associated, whereas several other tumors, such as Hodgkin's disease, nonHodgkin's lymphoma, lymphoepithelioma-like carcinoma, gastric adenocarcinoma, and several types of sarcoma, are less uniformly EBV-associated. 2-7 EBV causes benign transient lymphoproliferative lesions at the time of primary infection, and it is found in a benign lesion of the tongue called oral hairy leukoplakia. 8,9 Patients affected by these benign or malignant diseases may benefit from laboratory detection of EBV to confirm their diagnosis or to monitor disease burden after the initiation of therapy.Laboratory detection of EBV is accomplished in several ways (Table 1), and recent progress has focused on the molecular analysis of viral DNA and RNA. In situ hybridization has long been considered the gold standard for detecting tumor-associated viral infection, and EBV viral load assays are now being adopted for clinical evaluation of tumor burden in affected patients. This review article summarizes the pathobiology of EBV infection and describes the clinical laboratory tests that are used to assist in diagnosis and monitoring of patients with EBV-related diseases. The ...

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Detection of Epstein-Barr virus (EBV) genomes in the serum of patients with EBV-associated Hodgkin's disease

Cited by 151 publications

References 21 publications

Detection of cell free Epstein–Barr virus DNA in sera from patients with nasopharyngeal carcinoma

Detection of cell free Epstein–Barr virus DNA in sera from patients with nasopharyngeal carcinoma

Measuring Epstein–Barr virus (EBV) load: the significance and application for each EBV‐associated disease

Molecular Diagnosis of Epstein-Barr Virus-Related Diseases

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