The presence of JC virus in gastric carcinomas correlates with patient's age, intestinal histological type and aberrant methylation of tumor suppressor genes

JC virus (JCV) is a neurotropic polyomavirus and the causative agent of progressive multifocal leukoencephalopathy. A role for JCV in gastrointestinal malignancies has been recently suggested. This study was carried out to determine the prevalence of polyomaviruses including JCV, BKV and SV40 in gas...

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Veröffentlicht in:Modern pathology 2010-04, Vol.23 (4), p.522-530
Hauptverfasser: Ksiaa, Feryel, Ziadi, Sonia, Mokni, Moncef, Korbi, Sadok, Trimeche, Mounir
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description JC virus (JCV) is a neurotropic polyomavirus and the causative agent of progressive multifocal leukoencephalopathy. A role for JCV in gastrointestinal malignancies has been recently suggested. This study was carried out to determine the prevalence of polyomaviruses including JCV, BKV and SV40 in gastric cancers in Tunisia and to determine the clinicopathological characteristics of virus-associated gastric carcinomas. The presence of polyomaviruses DNA sequences was surveyed in 61 cases of primary gastric carcinomas and in 53 paired non-tumor gastric mucosa by PCR. Findings were correlated to clinicopathological parameters, p53 expression and methylation status of 11 tumor-related genes. Using PCR assays, JCV T-antigen sequence was more frequently detected in gastric carcinomas than in non-tumor gastric mucosa (26 vs 6%, P =0.03), while those of SV40 and BKV were not detected in any cases. Correlation analysis showed that JCV had higher frequency in patients older than 55 years ( P =0.034) and in the intestinal histological type ( P =0.04). With regard to methylation status, P16 and P14 showed significantly higher methylation frequencies in JCV-positive gastric carcinomas than in JCV-negative cases ( P =0.007 and P =0.003, respectively). Moreover, the mean of the methylation index was significantly higher in JCV-positive than in JCV-negative cases ( P =0.024). In multivariate logistic regression analysis, age of patients and the methylation index are only the two independent factors associated with JCV infection. Kaplan–Meier survival analysis showed a trend toward better survival for JCV-associated gastric carcinomas patients (log-rank, P =0.11). Our study suggests a role of JCV as cofactor in the pathogenesis of the intestinal type of gastric carcinomas in older persons.
doi_str_mv 10.1038/modpathol.2009.184
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A role for JCV in gastrointestinal malignancies has been recently suggested. This study was carried out to determine the prevalence of polyomaviruses including JCV, BKV and SV40 in gastric cancers in Tunisia and to determine the clinicopathological characteristics of virus-associated gastric carcinomas. The presence of polyomaviruses DNA sequences was surveyed in 61 cases of primary gastric carcinomas and in 53 paired non-tumor gastric mucosa by PCR. Findings were correlated to clinicopathological parameters, p53 expression and methylation status of 11 tumor-related genes. Using PCR assays, JCV T-antigen sequence was more frequently detected in gastric carcinomas than in non-tumor gastric mucosa (26 vs 6%, P =0.03), while those of SV40 and BKV were not detected in any cases. Correlation analysis showed that JCV had higher frequency in patients older than 55 years ( P =0.034) and in the intestinal histological type ( P =0.04). With regard to methylation status, P16 and P14 showed significantly higher methylation frequencies in JCV-positive gastric carcinomas than in JCV-negative cases ( P =0.007 and P =0.003, respectively). Moreover, the mean of the methylation index was significantly higher in JCV-positive than in JCV-negative cases ( P =0.024). In multivariate logistic regression analysis, age of patients and the methylation index are only the two independent factors associated with JCV infection. Kaplan–Meier survival analysis showed a trend toward better survival for JCV-associated gastric carcinomas patients (log-rank, P =0.11). 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With regard to methylation status, P16 and P14 showed significantly higher methylation frequencies in JCV-positive gastric carcinomas than in JCV-negative cases ( P =0.007 and P =0.003, respectively). Moreover, the mean of the methylation index was significantly higher in JCV-positive than in JCV-negative cases ( P =0.024). In multivariate logistic regression analysis, age of patients and the methylation index are only the two independent factors associated with JCV infection. Kaplan–Meier survival analysis showed a trend toward better survival for JCV-associated gastric carcinomas patients (log-rank, P =0.11). Our study suggests a role of JCV as cofactor in the pathogenesis of the intestinal type of gastric carcinomas in older persons.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>20081806</pmid><doi>10.1038/modpathol.2009.184</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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subjects 631/326/596
692/420
692/699/67/1504/1829
692/699/67/581
Adult
Age Factors
Aged
Aged, 80 and over
Antigens
Antigens, Viral, Tumor - isolation & purification
Cell cycle
DNA Methylation
Epigenetics
Female
Gastric cancer
Genes
Genes, Tumor Suppressor
Humans
Immunohistochemistry
JC virus
JC Virus - immunology
Kaplan-Meier Estimate
Laboratory Medicine
Male
Medicine
Medicine & Public Health
Middle Aged
original-article
Pathogenesis
Pathology
Polymerase Chain Reaction
Polyomavirus
Polyomavirus Infections - complications
Promoter Regions, Genetic - genetics
Simian virus 40
Stomach Neoplasms - genetics
Stomach Neoplasms - pathology
Stomach Neoplasms - virology
Survival analysis
Tumor Virus Infections - complications
Tumors
title The presence of JC virus in gastric carcinomas correlates with patient's age, intestinal histological type and aberrant methylation of tumor suppressor genes
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