EBV Viral Load in Tumor Tissue Is an Important Prognostic Indicator for Nasal NK/T-Cell Lymphoma

Hsieh, Pin‐Pen; Tung, Chun Liang; Chan, Amy Bik Wan; Liao, Jia Bin; Wang, Jyh Seng; Tseng, Hui‐Hsin; Su, Hsing Hao; Chang, Kun Chao; Chang, Chung Che

doi:10.1309/mn4y8hlqwkd9nb5e

Cited by 37 publications

(46 citation statements)

References 28 publications

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“…High viral DNA copy numbers have often been linked to poor prognoses in cancers associated with viral infections (2,4,7,13,15,20,33,62). Exceptions to this paradigm include infections that result in integrated viral genomes (9).…”

Section: Discussionmentioning

confidence: 99%

Genetic Analysis of Cytomegalovirus in Malignant Gliomas

Bhattacharjee

Renzette

Kowalik

2012

J Virol

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Human cytomegalovirus (HCMV) has been found in malignant gliomas at variable frequencies with efforts to date focused on characterizing the role(s) of single gene products in disease. Here, we reexamined the HCMV prevalence in malignant gliomas using different methods and began to dissect the genetics of HCMV in tumors. HCMV DNA was found in 16/17 (94%) tumor specimens. Viral DNA copy numbers were found to be low and variable, ranging from 10 2 to 10 6 copies/500 ng of total DNA. The tumor tissues had incongruences between viral DNA copy numbers and protein levels. However, nonlatent protein expression was detected in many tumors. The viral UL83 gene, encoding pp65, was found to segregate into five cancer-associated genotypes with a bias for amino acid changes in glioblastoma multiforme (GBM) in comparison to the low-grade tumors. Deep sequencing of a GBM-associated viral population resulted in 81,224 bp of genome coverage. Sequence analysis revealed the presence of intact open reading frames and higher numbers of high-frequency variations within the repeat long region compared to the unique long region, which harbors many core genes, and the unique short region ( P = 0.001). This observation was in congruence with phylogenetic analyses across replication-competent viral strains in databases. The tumor-associated viral population was less variable (π = 0.1% and π AA = 0.08%) than that observed in other clinical infections. Moreover, 42/46 (91.3%) viral genes analyzed had dN/dS scores of <1, which is indicative of high amino acid sequence conservation. Taken together, these findings raise the possibility that replication-competent HCMV may exist in malignant gliomas.

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Section: Discussionmentioning

confidence: 99%

Genetic Analysis of Cytomegalovirus in Malignant Gliomas

Bhattacharjee

Renzette

Kowalik

2012

J Virol

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“…The detection of EBV in sites where it is usually absent, such as the liver or bone marrow, can help in diagnosis of extranodal involvement. Elevated levels of EBV DNA in serum or tumor tissue have correlated with a poor prognosis in ENKL, nasal-type [9]. Immunophenotypic variants, which lack EBV or CD56 or which express CD30, can contribute to problems in diagnosis, as there is often an overlap with peripheral T-cell lymphomas, not otherwise specifi ed [8••].…”

Section: Pathology and Geneticsmentioning

confidence: 99%

Natural killer-cell neoplasms

Greer

Mosse²

2009

Curr Hematol Malig Rep

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The natural killer (NK)-cell neoplasms are rare, representing less than 1% of non-Hodgkin lymphoma, except in Asia and Latin America, where they represent 3% to 6%. NK-cell neoplasms include immature acute leukemias; a blastic NK-cell lymphoma, which is obsolete because of its plasmacytoid dendritic-cell origin; and mature NK neoplasms, comprising extranodal NK/T-cell lymphoma (ENKL), nasal-type; aggressive NK-cell leukemia; and chronic NK-cell lymphoproliferative disorders, which are often reactive. Epstein-Barr virus is usually detected in tumor cells of ENKL and aggressive NK-cell leukemia. The latter two mature NK neoplasms are relatively chemoresistant because of the frequent expression of P-glycoprotein. Early radiation is advocated for localized nasal ENKL. Stem cell transplantation is recommended for advanced disease, owing to a poor prognosis. Novel agents, including chemotherapy, inhibitors of molecular pathways, and monoclonal antibodies, are under investigation.

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“…In hepatocellular carcinoma, a low serum viral load of hepatitis B virus DNA at the diagnosis was associated with an improved survival rate of the patients (Ohkubo et al, 2002). In nasal NK/Tcell lymphoma, a low viral load of Epstein-Barr virus detected in formalin-fixed paraffin-embedded tissue was reported to be associated with better overall survival of the patients, compared to the high viral load (Hsieh et al, 2007). The prognostic value of HPV viral load has been evaluated in studies on HPV-associated cancers such as tonsillar squamous cell carcinoma and cervical carcinoma (Mellin et al, 2002;Datta et al, 2006;de Boer et al, 2007;Cohen et al, 2008;Kim et al, 2008Kim et al, : 2009Gnanamony et al, 2009;Kang et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of HPV18 DNA Viral Load in Patients with Early-Stage Neuroendocrine Carcinoma of the Uterine Cervix

Siriaunkgul

Utaipat²,

Suwiwat³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Objectives: To evaluate the clinicopathologic correlation and prognostic value of HPV18 DNA viral load in patients with early-stage cervical neuroendocrine carcinoma (NECA). Methods: Formalin-fixed, paraffinembedded tissue of cervical NECA patients with known HPV18 infection and clinicopathologic data including follow-up results were collected. The HPV18 DNA load was assessed with quantitative PCR targeting the HPV18 E6E7 region. Results: Twenty-one patients with early-stage (IB-IIA) cervical NECA were identified. HPV18 DNA viral load ranged from 0.83 to 55,174 copies/cell (median 5.90). Disease progression, observed in 10 cases (48%), was not significantly associated with any clinicopathologic variables. However, the group of patients with progressive disease tended to have a higher rate of pelvic lymph node metastasis (50% versus 9%, p=0.063) and a lower median value of HPV18 DNA viral load (4.37 versus 8.17 copies/cell, p=0.198) compared to the non-recurrent group. When stratified by a cut-off viral load value of 5.00 copies/cell, the group of patients with viral load ≤5.00 copies/cell had a significantly shorter disease-free survival than the group with viral load >5.00 copies/cell (p=0.028). The group with a lower viral load also tended to have a higher rate of disease progression (75% versus 31%, p=0.080). No significant difference in the other clinicopathologic variables between the lower and higher viral load groups was identified. Conclusion: HPV18 DNA viral load may have a prognostic value in patients with early-stage NECA of the cervix. A low viral load may be predictive of shortened disease-free survival in these patients.

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EBV Viral Load in Tumor Tissue Is an Important Prognostic Indicator for Nasal NK/T-Cell Lymphoma

Cited by 37 publications

References 28 publications

Genetic Analysis of Cytomegalovirus in Malignant Gliomas

Genetic Analysis of Cytomegalovirus in Malignant Gliomas

Natural killer-cell neoplasms

Prognostic Value of HPV18 DNA Viral Load in Patients with Early-Stage Neuroendocrine Carcinoma of the Uterine Cervix

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