scholarly journals Epstein–Barr Virus (EBV) Viral Load in Tumor Cells Did Not Predict Tumor Extensiveness in Nasopharyngeal Cancer

2021 ◽  
Vol 12 (1) ◽  
pp. 150-156
Author(s):  
Soehartati A. Gondhowiardjo ◽  
Handoko ◽  
Marlinda Adham ◽  
Lisnawati Rachmadi ◽  
Henry Kodrat ◽  
...  

Background: Nasopharyngeal cancer is commonly associated with Epstein–Barr virus (EBV) infection, especially undifferentiated non-keratinized histology. EBV DNA quantification through nasopharyngeal brushing was previously reported to be not related to disease stage. This study aimed to reinvestigate the relationship of EBV viral load in tumor tissue with tumor extensiveness by more accurate EBV DNA quantification through microscopically confirmed tumor cells from nasopharyngeal biopsy. Method: The specimens for EBV DNA quantification were derived from histopathology slides which were pre-treated following the QIAsymphony® SP protocol for tissue DNA extraction. Then, the extracted DNA underwent real-time polymerase chain reaction (RT-PCR) using the artus® EBV RG PCR Kit for EBV DNA quantification. The tumor volume was determined by delineating the gross tumor based on 3D imaging of the patient’s nasopharynx. Result: Twenty-four subjects were included in this study. All subjects were stage III and above, with more males (75%) than females. EBV viral load in tumor cells was found to have no correlation to tumor volume both in local and nodal regions. The median local tumor volume was 81.3 cm3 ± 80 cm3. The median EBV viral load in tumor cells was 95,644.8 ± 224,758.4 copies/100 ng of DNA. The median nodal or regional tumor volume was 35.7 ± 73.63 cm3. Conclusion: EBV viral load from tumor cells from nasopharyngeal biopsy has no relationship with tumor extensiveness in nasopharyngeal cancer. The presence and amount of EBV in tumor cells did not translate into larger or smaller tumors. The EBV viral proteins and RNAs were perhaps more likely to confer some prognostic information due to the fact that those molecules were related to carcinogenesis.

2020 ◽  
Author(s):  
Soehartati A Gondhowiardjo ◽  
Handoko Handoko ◽  
Marlinda Adham ◽  
Lisnawati Rachmadi ◽  
Henry Kodrat ◽  
...  

Abstract Background:Nasopharyngeal cancer is commonly associated with EBV infection, especially the undifferentiated non keratinized histology. EBV DNA quantification through nasopharyngeal brushing was previously reported not related with disease stages. This study aimed to reinvestigate relationship of EBV viral load in tumor tissue with tumor extensiveness by more accurate EBV DNA quantification through microscopically confirmed tumor cells from nasopharyngeal biopsy. Method:The specimens for EBV DNA quantification was derived from histopathology slides which was pre-treated following QIAsymphony® SP Protocol for tissue DNA extraction. Then the extracted DNA underwent real time Polymerase Chain Reaction (RT-PCR) using artus® EBV RG PCR Kit for EBV DNA quantification. The tumor volume was determined by delineating gross tumor based on 3D imaging of the patient’s nasopharynx.Result:Twenty-four subjects were included in this study. All subjects were stage III and above with more males (75%) than females. EBV viral load in tumor cells were found to have no correlation with tumor volume both in local and nodal. The median local tumor volume was 81.3 cm3 ± 80 cm3. The median EBV viral load in tumor cells was 95,644.8 copies/100ng of DNA ± 224,758.4 copies/100ng of DNA. The median nodal or regional tumor volume was 35.7 cm3 ± 73.63 cm3.Conclusion:EBV viral load from tumor cells from nasopharyngeal biopsy has no relationship with tumor extensiveness in nasopharyngeal cancer. The presence and number of EBV in tumor cells did not translate into larger or smaller tumor. The EBV viral proteins and RNAs were perhaps more likely to confer some prognostic information due to the facts that those molecules were related with carcinogenesis.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17543-e17543 ◽  
Author(s):  
Aysel Ahmedova ◽  
Kubra Ozkaya ◽  
Makbule Tambas ◽  
Ugur Gezer ◽  
Emre Ozgur ◽  
...  

e17543 Background: To investigate the relationship between pretreatment Epstein-Barr virus (EBV) DNA copy number and tumor metabolic activity, TNM stage and tumor volume in nasopharyngeal cancer (NPC) patients. Methods: Blood samples were collected 0-3 weeks before treatment and number of EBV DNA copies were determined by PCR . MRI and PET-CT were performed 0-4 weeks before treatment. The primary tumor volume (TVnp) and total volume of metastatic lymph nodes (TLV) were delineated separately on MRI by the same radiologist by the aid of program “Osirix” and recorded in cm3. Maximum SUV values of primary tumor (Tsuv) and metastatic lymph nodes (LNsuv) were determined with each PET-CT images. Kruskal Wallis test and Spearman's Correlation Analysis were used for the comparison of 3 or more groups with no normal distribution and the evaluation of the inter-parameter relations, respectively. Results: The study included 50 NPC patients treated between 2011 and 2015. There was no significant relation between serum EBV DNA copy number and the distribution of T stage (p = 0.81), N stage (p = 0.08), TVnp (r:0.009; p = 0.95), and Tsuv (r:-0.007, p = 0.96). However, a significant correlation was detected between EBV DNA copy number and both LNsuv (r:0.337; p = 0.017) and TLV (r:0.579; p = 0.001) (LNsuv and TLV increased as virus load increased). Conclusions: There is no significant relation between pretreatment EBV DNA load and T and N stages and TVnp in NPC patients. However, EBV DNA load has a significant correlation with TLV and LNsuv. These results may imply that TLV can be included in nodal staging and together with LNsuv be integrated in treatment planning.[Table: see text] [Table: see text]


Blood ◽  
1993 ◽  
Vol 81 (10) ◽  
pp. 2688-2695 ◽  
Author(s):  
P Kanavaros ◽  
MC Lescs ◽  
J Briere ◽  
M Divine ◽  
F Galateau ◽  
...  

Recent evidence has shown that most nasal lymphomas (NL) are associated with a T-cell phenotype and are thus called nasal T-cell lymphomas (NTCL), but little information is available about the T-cell receptor (TCR) expression. The presence of Epstein-Barr virus (EBV) genome has been recently reported in NTCL in Oriental populations in which NL and EBV-associated tumors are more common and in occasional Occidental cases. This prompted us to investigate lymphoma biopsies from 7 non- Oriental patients with NTCL for the expression of natural killer (NK) and T-cell antigens, including TCR proteins, for the presence of EBV- encoded latent membrane protein (LMP) using immunohistochemistry and for the presence of EBV DNA and Epstein-Barr early region (EBER) RNA using in situ hybridization (ISH). Six cases displayed a CD3-, TCR alpha beta-, TCR gamma delta-, CD2+, CD7+, CD5-, CD4-, CD8-, CD56+ phenotype, suggesting that these tumors may be peripheral T-cell lymphomas (PTCL) with extensive loss of T-cell antigens and expression of the NK-cell (CD56) antigen or, alternatively, NK-cell neoplasias. The remaining case was a gamma delta PTCL, as shown by the CD3+, TCR gamma delta+ phenotype and the biallelic gamma and delta TCR gene rearrangements. Using ISH, EBER RNA transcripts were detected in tumor cells in all cases and EBV DNA was shown in the 6 tested cases. In all cases, tumor cells expressed LMP. These findings support the concept that NTCL constitute a distinct group of lymphomas that, in addition to their peculiar clinical features, exhibit an unusual TCR “silent” CD56+ or TCR gamma delta+ phenotype and harbor the EBV. In view of the LMP transforming potential, these data suggest that EBV may play a role in the pathogenesis of NTCL.


2021 ◽  
Vol 8 (3) ◽  
pp. 14-24
Author(s):  
K. V. Smirnova ◽  
N. B. Senuta ◽  
I. V. Botezatu ◽  
A. V. Ignatova ◽  
T. E. Dushenkina ◽  
...  

Introduction. Epstein–Barr virus (EBV) is equally widespread in the endemic and non-endemic world regions for nasopharyngeal cancer (NPC). High incidence of NPC in endemic countries and low in non-endemic countries suggest there are different mechanisms and conditions for tumor occurrence and, possibly, different clinical significance of EBV-associated markers. However, significance of these markers for determining NPC in non-endemic regions is still poorly understood. Objective – to determine clinical significance of titers of IgG/IgA antibodies to EBV capsid antigen and concentrations of the viral DNA in patients’ blood plasma as diagnostic and monitoring markers for NPC in a non-endemic region of Russia. Materials and methods. Titers of EB-specific antibodies were determined by indirect immunofluorescence, and concentration of the viral DNA in plasma was measured using a quantitative polymerase chain reaction in real time. Study group included patients with NPC (n = 96), and control group – blood donors (n = 171) and patients with other head and neck tumors (n = 33).Results. Titers of IgG/IgA antibodies to EBV capsid antigen, being an important diagnostic marker of nasopharyngeal cancer, did not always correlate with patients’ clinical condition. Humoral response to emerging events often delayed due to inertia of the immune system. Concentration of EBV DNA in patients’ blood plasma clearly reflected the dynamics of the pathological process: it decreased to background values in remission and increased while the disease progressed. In contrast to endemic regions, we did not find any correlation between the studied EBV markers and clinical manifestations of the disease, evaluated in accordance with the TNM classification (Tumor, Nodus and Metastasis).Conclusion. In non-endemic countries, such as Russia, serological and molecular markers of EBV can be successfully used for the primary diagnosis of NPC. However, for the disease monitoring, it is preferable to use the value of the concentrations of circulating EBV DNA, which, in contrast to the values of IgG/IgA antibody titers to VCA EBV, more accurately reflect the patient’s clinical condition.


Blood ◽  
1993 ◽  
Vol 81 (10) ◽  
pp. 2688-2695 ◽  
Author(s):  
P Kanavaros ◽  
MC Lescs ◽  
J Briere ◽  
M Divine ◽  
F Galateau ◽  
...  

Abstract Recent evidence has shown that most nasal lymphomas (NL) are associated with a T-cell phenotype and are thus called nasal T-cell lymphomas (NTCL), but little information is available about the T-cell receptor (TCR) expression. The presence of Epstein-Barr virus (EBV) genome has been recently reported in NTCL in Oriental populations in which NL and EBV-associated tumors are more common and in occasional Occidental cases. This prompted us to investigate lymphoma biopsies from 7 non- Oriental patients with NTCL for the expression of natural killer (NK) and T-cell antigens, including TCR proteins, for the presence of EBV- encoded latent membrane protein (LMP) using immunohistochemistry and for the presence of EBV DNA and Epstein-Barr early region (EBER) RNA using in situ hybridization (ISH). Six cases displayed a CD3-, TCR alpha beta-, TCR gamma delta-, CD2+, CD7+, CD5-, CD4-, CD8-, CD56+ phenotype, suggesting that these tumors may be peripheral T-cell lymphomas (PTCL) with extensive loss of T-cell antigens and expression of the NK-cell (CD56) antigen or, alternatively, NK-cell neoplasias. The remaining case was a gamma delta PTCL, as shown by the CD3+, TCR gamma delta+ phenotype and the biallelic gamma and delta TCR gene rearrangements. Using ISH, EBER RNA transcripts were detected in tumor cells in all cases and EBV DNA was shown in the 6 tested cases. In all cases, tumor cells expressed LMP. These findings support the concept that NTCL constitute a distinct group of lymphomas that, in addition to their peculiar clinical features, exhibit an unusual TCR “silent” CD56+ or TCR gamma delta+ phenotype and harbor the EBV. In view of the LMP transforming potential, these data suggest that EBV may play a role in the pathogenesis of NTCL.


2019 ◽  
Vol 57 (5) ◽  
pp. 759-765 ◽  
Author(s):  
Wang Kedi ◽  
Xu Dongjiang ◽  
Lv Zhi ◽  
Gao Yan ◽  
Jia Kun ◽  
...  

Abstract Background Epstein-Barr virus (EBV) DNA load monitoring in blood is essential for the diagnosis of EBV-associated diseases. However, the best-suited blood compartment for detection is still under discussion. The aim of this study was to evaluate the diagnostic value of EBV-DNA load in peripheral blood mononuclear cells (PBMC), plasma and whole blood (WB) samples. Methods A total of 156 patients, including 45 patients with infectious mononucleosis (IM), 57 patients with EBV-associated hemophagocytic lymphohistiocytosis (HLH) and 54 patients with post-transplant lymphoproliferative disorders (PTLD), were enrolled in this study. The EBV-DNA load in PBMC, plasma and WB samples were measured with real-time quantitative polymerase chain reaction (PCR). Results EBV-DNA load of patients with HLH showed no statistical difference in PBMC, plasma and WB samples, while patients with IM and PTLD showed a higher viral load in PBMC samples. The strongest correlation of EBV-DNA level was found between PBMC and WB samples among patients with IM, HLH and PTLD. The follow-up of EBV-DNA showed that the viral load became negative along with the recovery from the disease, while that in WB and PBMC would remain positive for a long time. Conclusions For the diagnosis and monitoring of EBV-DNA, the type of specimen should be chosen reasonably according to the disease. As for IM and HLH, plasma is recommended to quantify the EBV-DNA load, while PBMC and plasma are preferred in PTLD.


2019 ◽  
Vol 49 (12) ◽  
pp. 1100-1113 ◽  
Author(s):  
Sarin Kitpanit ◽  
Nutchawan Jittapiromsak ◽  
Aniwat Sriyook ◽  
Anussara Prayongrat ◽  
Danita Kannarunimit ◽  
...  

The eighth AJCC/UICC staging for nasopharyngeal cancer had higher prognostic values than the previous edition. Pretreatment plasma EBV DNA integrated into the next edition could further improve the outcome prediction.


2018 ◽  
Vol 36 (31) ◽  
pp. 3091-3100 ◽  
Author(s):  
Anthony T.C. Chan ◽  
Edwin P. Hui ◽  
Roger K.C. Ngan ◽  
Stewart Y. Tung ◽  
Ashley C.K. Cheng ◽  
...  

Purpose The contribution of adjuvant chemotherapy after chemoradiation therapy (CRT) in nasopharyngeal cancer (NPC) remains controversial. Plasma Epstein-Barr virus (EBV) DNA is a potential biomarker of subclinical residual disease in NPC. In this prospective, multicenter, randomized controlled trial, we used plasma EBV DNA to identify patients with NPC at a higher risk of relapse for adjuvant chemotherapy. Patients and Methods Eligible patients with histologically confirmed NPC of Union for International Cancer Control stage IIB to IVB, adequate organ function, and no locoregional disease or distant metastasis were screened by plasma EBV DNA at 6 to 8 weeks after radiotherapy (RT). Patients with undetectable plasma EBV DNA underwent standard surveillance. Patients with detectable plasma EBV DNA were randomly assigned to either adjuvant chemotherapy with cisplatin and gemcitabine for six cycles (arm 1) or observation (arm 2). Patients were stratified for primary treatment (RT v CRT) and stage (II/III v IV). The primary end point was relapse-free survival (RFS). Results Seven hundred eighty-nine patients underwent EBV DNA screening. Plasma EBV DNA was undetectable in 573 (72.6%) and detectable in 216 (27.4%); 104 (13.2%) with detectable EBV DNA were randomly assigned to arms 1 (n = 52) and 2 (n = 52). After a median follow-up of 6.6 years, no significant difference was found in 5-year RFS rate between arms 1 and 2 (49.3% v 54.7%; P = .75; hazard ratio for relapse or death, 1.09; 95% CI, 0.63 to 1.89). The level of post-RT plasma EBV DNA correlated significantly with the hazards of locoregional failure, distant metastasis, and death. Conclusion In patients with NPC with detectable post-RT plasma EBV DNA, adjuvant chemotherapy with cisplatin and gemcitabine did not improve RFS. Post-RT plasma EBV DNA level should be incorporated as the selection factor in future clinical trials of adjuvant therapy in NPC.


2011 ◽  
Vol 17 (9) ◽  
pp. 2885-2892 ◽  
Author(s):  
Stefan Hohaus ◽  
Rosaria Santangelo ◽  
Manuela Giachelia ◽  
Barbara Vannata ◽  
Giuseppina Massini ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Qiao Li ◽  
TingTing Wang ◽  
Yan Huang ◽  
Qin Li ◽  
PeiYao Liu ◽  
...  

Purpose: We aimed to investigate whether Epstein–Barr virus (EBV) could produce differences on MRI by examining the histogram and texture imaging features. We also sought to determine the predictive value of pretreatment MRI texture analyses incorporating with EBV status for disease progression (PD) in patients with primary nasopharyngeal carcinoma (NPC).Materials and Methods: Eighty-one patients with primary T2-T4 NPC and known EBV status who underwent contrast-enhanced MRI were included in this retrospective study. Whole-tumor-based histogram and texture features were extracted from pretreatment T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and contrast-enhanced (CE)-T1WI images. Mann–Whitney U-tests were performed to identify the differences in histogram and texture parameters between EBV DNA-positive and EBV DNA-negative NPC images. The effects of clinical variables as well as histogram and texture features were estimated by using univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was used to predict the EBV status and PD. Finally, an integrated model with the best performance was built.Results: Of the 81 patients included, 54 had EBV DNA-positive NPC, and 27 had EBV DNA-negative NPC. Patients who were tested EBV DNA-positive had higher overall stage (P = 0.016), more lymphatic metastases (p < 0.0001), and easier distant metastases (P = 0.026) than the patients who were tested EBV DNA-negative. Tumor volume, T1WISkewness and T2WIKurtosis showed significant differences between the two groups. The combination of the three features achieved an AUC of 0.783 [95% confidence interval (CI) 0.678–0.888] with a sensitivity and specificity of 70.4 and 74.1%, respectively, in differentiating EBV DNA-positive tumors from EBV DNA-negative tumors. The combination of overall stage and tumor volume of T2WIKurtosis and EBV status was the most effective model for predicting PD in patients with primary NPC. The overall accuracy was 84.6%, with a sensitivity and specificity of 93.8 and 66.2%, respectively (AUC, 0.800; 95% CI 0.700–0.900).Conclusion: This study demonstrates that MRI-based radiological features and EBV status can be used as an aid tool for the evaluation of PD, in order to develop tailored treatment targeting specific characteristics of individual patients.


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