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      Human polyomaviruses JCPyV and MCPyV in urothelial cell carcinoma: a single institution experience

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          Abstract

          Objective

          Urothelial cell carcinoma (UCC) is the most common type of urinary bladder. JCPyV and BKPyV have been detected in the urine and tissue of urothelial cell carcinomas (UCC) in immunocompetent patients. Here, we investigated the presence of several HPyVs in UCC samples using diverse molecular techniques to study the prevalence of HPyVs in UCC.

          Methods

          A large single-institution database of urine cytology specimens (UCS; n = 22.867 UCS) has previously been searched for decoy cells ( n = 30), suggesting polyomavirus infection. The available urine sediments and formalin-fixed paraffin-embedded (FFPE) tissue samples of UCC patients were tested for the presence of JCPyV-LTAg expression by immunohistochemistry (IHC) labeled with SV40-LTAg antibody (clone: PAb416) and subsequent PCR followed by sequencing. In addition, the presence of the oncogenic Merkel cell polyomavirus (MCPyV) and the presence of human polyomavirus 6 (HPyV6) and 7 (HPyV7) DNA were tested with DNA PCR or IHC.

          Results

          Of the 30 patients harboring decoy cells, 14 were diagnosed with UCC of the urinary bladder (14/30; 46.6%) before presenting with decoy cells in the urine. The SV40-LTAg IHC was positive in all 14 UCC urine sediments and negative in the FFPE tissues. JCPyV-DNA was identified in all five available UCS and in three FFPE samples of UCC (three of 14; 21.4%). Two UCC cases were positive for MCPyV-DNA (two of 14; 14.3%), and one of them showed protein expression by IHC (one of 14; 7.1%). All specimens were HPyV6 and HPyV7 negative.

          Conclusion

          Our findings show the presence of JCPyV in the urine and UCC of immunocompetent patients. Moreover, MCPyV was detected in two UCC cases. In total, five UCC cases showed the presence of either JCPyV or MCPyV. The evidence here supports the hypothesis that these viruses might sporadically be associated with UCC. Further studies are needed to confirm the relevance of JCPyV or MCPyV as a possible risk factor for UCC development.

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          Most cited references57

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          Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012.

          Estimates of the worldwide incidence and mortality from 27 major cancers and for all cancers combined for 2012 are now available in the GLOBOCAN series of the International Agency for Research on Cancer. We review the sources and methods used in compiling the national cancer incidence and mortality estimates, and briefly describe the key results by cancer site and in 20 large "areas" of the world. Overall, there were 14.1 million new cases and 8.2 million deaths in 2012. The most commonly diagnosed cancers were lung (1.82 million), breast (1.67 million), and colorectal (1.36 million); the most common causes of cancer death were lung cancer (1.6 million deaths), liver cancer (745,000 deaths), and stomach cancer (723,000 deaths). © 2014 UICC.
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            Cancer statistics, 2015.

            Each year the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the National Cancer Institute (Surveillance, Epidemiology, and End Results [SEER] Program), the Centers for Disease Control and Prevention (National Program of Cancer Registries), and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistics. A total of 1,658,370 new cancer cases and 589,430 cancer deaths are projected to occur in the United States in 2015. During the most recent 5 years for which there are data (2007-2011), delay-adjusted cancer incidence rates (13 oldest SEER registries) declined by 1.8% per year in men and were stable in women, while cancer death rates nationwide decreased by 1.8% per year in men and by 1.4% per year in women. The overall cancer death rate decreased from 215.1 (per 100,000 population) in 1991 to 168.7 in 2011, a total relative decline of 22%. However, the magnitude of the decline varied by state, and was generally lowest in the South (∼15%) and highest in the Northeast (≥20%). For example, there were declines of 25% to 30% in Maryland, New Jersey, Massachusetts, New York, and Delaware, which collectively averted 29,000 cancer deaths in 2011 as a result of this progress. Further gains can be accelerated by applying existing cancer control knowledge across all segments of the population. © 2015 American Cancer Society.
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              Clonal integration of a polyomavirus in human Merkel cell carcinoma.

              Merkel cell carcinoma (MCC) is a rare but aggressive human skin cancer that typically affects elderly and immunosuppressed individuals, a feature suggestive of an infectious origin. We studied MCC samples by digital transcriptome subtraction and detected a fusion transcript between a previously undescribed virus T antigen and a human receptor tyrosine phosphatase. Further investigation led to identification and sequence analysis of the 5387-base-pair genome of a previously unknown polyomavirus that we call Merkel cell polyomavirus (MCV or MCPyV). MCV sequences were detected in 8 of 10 (80%) MCC tumors but only 5 of 59 (8%) control tissues from various body sites and 4 of 25 (16%) control skin tissues. In six of eight MCV-positive MCCs, viral DNA was integrated within the tumor genome in a clonal pattern, suggesting that MCV infection and integration preceded clonal expansion of the tumor cells. Thus, MCV may be a contributing factor in the pathogenesis of MCC.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                13 December 2023
                2023
                : 13
                : 1251244
                Affiliations
                [1] 1 Department of Pathology, GROW-School for Oncology and Reproduction, Maastricht University, Medical Centre+ , Maastricht, Netherlands
                [2] 2 Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Al-Baha University , Al-Baha, Saudi Arabia
                [3] 3 Department of Medical Laboratories Technology, Faculty of Applied Medical Sciences, Jazan University , Jazan, Saudi Arabia
                [4] 4 Department of Urology, Maastricht University, Medical Centre+ , Maastricht, Netherlands
                [5] 5 Pathology Department, Faculty of Medicine, Jazan University , Jazan, Saudi Arabia
                Author notes

                Edited by: Fernanda Martini, University of Ferrara, Italy

                Reviewed by: Luis Del Valle, Louisiana State University, United States

                John Charles Rotondo, University of Ferrara, Italy

                *Correspondence: Iryna Samarska, Iryna.samarska@ 123456mumc.nl ; Faisal Klufah, fklufah@ 123456bu.edu.sa

                †These authors share first authorship

                Article
                10.3389/fonc.2023.1251244
                10773619
                38192628
                a464536d-65aa-4a6c-8976-509aed29b05e
                Copyright © 2023 Klufah, Mobaraki, Shi, Marcelissen, Alharbi, Mobarki, Almalki, van Roermund, zur Hausen and Samarska

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 01 July 2023
                : 27 November 2023
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 57, Pages: 9, Words: 3945
                Funding
                The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.
                Categories
                Oncology
                Original Research
                Custom metadata
                Molecular and Cellular Oncology

                Oncology & Radiotherapy
                jcpyv,bladder cancer,polyomavirus,tumorigenesis,decoy cells,hpyv6,hpyv7,mcpyv
                Oncology & Radiotherapy
                jcpyv, bladder cancer, polyomavirus, tumorigenesis, decoy cells, hpyv6, hpyv7, mcpyv

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