{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:43:24Z","timestamp":1760233404063,"version":"build-2065373602"},"reference-count":28,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T00:00:00Z","timestamp":1609804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["RM11916B1DFD19A1"],"award-info":[{"award-number":["RM11916B1DFD19A1"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Because the incidence of Merkel cell carcinoma (MCC) has increased significantly during the last 10 years and it is recognized that Merkel cell polyomavirus (MCPyV) and ultraviolet (UV) radiation represent two different etiological inputs sharing clinical, histopathological, and prognostic similar features, although with different prognosis, this study investigated the detection of MCPyV in skin and lymph nodes with histological diagnosis of MCC. Formalin-fixed paraffin-embedded tissue (FFPE) were retrieved from archived specimens and MCPyV non-coding control region (NCCR) and viral capsid protein 1 (VP1) sequences were amplified and sequenced. Results provide an interesting observation concerning the discrepancy between the MCPyV DNA status in primary and metastatic sites: in fact, in all cases in which primary and metastatic lesions were investigated, MCPyV DNA was detected only in the primary lesions. Our data further support the \u201chit-and-run\u201d theory, also proposed by other authors, and may lead to speculation that in some MCCs the virus is only necessary for the process of tumor initiation and that further mutations may render the tumor independent from the virus. Few point mutations were detected in the NCCR and only silent mutations were observed in the VP1 sequence compared to the MCPyV MCC350 isolate. To unequivocally establish a role of MCPyV in malignancies, additional well-controlled investigations are required, and larger cohorts should be examined.<\/jats:p>","DOI":"10.3390\/v13010061","type":"journal-article","created":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T11:51:39Z","timestamp":1609847499000},"page":"61","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Evaluation of Merkel Cell Polyomavirus DNA in Tissue Samples from Italian Patients with Diagnosis of MCC"],"prefix":"10.3390","volume":"13","author":[{"given":"Carla","family":"Prezioso","sequence":"first","affiliation":[{"name":"Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy"},{"name":"Microbiology of Chronic Neuro-degenerative Pathologies, IRCSS San Raffaele Pisana, 00163 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raffaella","family":"Carletti","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Obregon","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Piacentini","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Maria","family":"Manicone","sequence":"additional","affiliation":[{"name":"Division of Pathology, \u201cS.M. Goretti\u201d Hospital, 04100 Latina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Soda","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ugo","family":"Moens","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Health Sciences, University of Troms\u00f8, The Arctic University of Norway, 9037 Troms\u00f8, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4696-0560","authenticated-orcid":false,"given":"Cira","family":"Di Gioia","sequence":"additional","affiliation":[{"name":"Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5723-8886","authenticated-orcid":false,"given":"Valeria","family":"Pietropaolo","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Pietropaolo, V., Prezioso, C., and Moens, U. (2020). Merkel Cell Polyomavirus and Merkel Cell Carcinoma. Cancers, 12.","DOI":"10.3390\/cancers12071774"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1146\/annurev-virology-011720-121757","article-title":"Molecular Mechanisms of Merkel Cell Polyomavirus Transformation and Replication","volume":"7","author":"Liu","year":"2020","journal-title":"Annu. Rev. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Pastrana, D.V., Tolstov, Y.L., Becker, J.C., Moore, P.S., Chang, Y., and Buck, C.B. (2009). Quantitation of human seroresponsiveness to Merkel cell polyomavirus. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000578"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1146\/annurev-pathol-011110-130227","article-title":"Merkel cell carcinoma: A virus-induced human cancer","volume":"7","author":"Chang","year":"2012","journal-title":"Annu. Rev. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1126\/science.1152586","article-title":"Clonal integration of a polyomavirus in human Merkel cell carcinoma","volume":"319","author":"Feng","year":"2008","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1097\/PAP.0b013e3181a12f5a","article-title":"Merkel cell carcinoma: Review","volume":"16","author":"Pulitzer","year":"2009","journal-title":"Adv. Anat. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/modpathol.2015.154","article-title":"Next generation sequencing of Cytokeratin 20-negative Merkel cell carcinoma reveals ultraviolet-signature mutations and recurrent TP53 and RB1 inactivation","volume":"29","author":"Harms","year":"2016","journal-title":"Mod. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3720","DOI":"10.1158\/0008-5472.CAN-15-0702","article-title":"The Distinctive Mutational Spectra of Polyomavirus-Negative Merkel Cell Carcinoma","volume":"75","author":"Harms","year":"2015","journal-title":"Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.jid.2016.08.015","article-title":"Shared Oncogenic Pathways Implicated in Both Virus-Positive and UV-Induced Merkel Cell Carcinomas","volume":"137","author":"Derdak","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5961","DOI":"10.1158\/1078-0432.CCR-18-4159","article-title":"The Genomic Landscape of Merkel Cell Carcinoma and Clinicogenomic Biomarkers of Response to Immune Checkpoint Inhibitor Therapy","volume":"25","author":"Knepper","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"17077","DOI":"10.1038\/nrdp.2017.77","article-title":"Merkel cell carcinoma","volume":"3","author":"Becker","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.path.2017.01.013","article-title":"Merkel Cell Carcinoma","volume":"10","author":"Pulitzer","year":"2017","journal-title":"Surg. Pathol. Clin."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1093\/jnci\/djp139","article-title":"Clinical factors associated with Merkel cell polyomavirus infection in Merkel cell carcinoma","volume":"101","author":"Sihto","year":"2009","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/324163a0","article-title":"Analysis of enzymatically amplified beta-globin and HLA-DQ alpha DNA with allele-specific oligonucleotide probes","volume":"324","author":"Saiki","year":"1986","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4645","DOI":"10.1172\/JCI64116","article-title":"Improved detection suggests all Merkel cell carcinomas harbour Merkel polyomavirus","volume":"122","author":"Rodig","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Prezioso, C., Obregon, F., Ambroselli, D., Petrolo, S., Checconi, P., Rodio, D.M., Coppola, L., Nardi, A., Vito, C., and Sarmati, L. (2020). Merkel Cell Polyomavirus (MCPyV) in the Context of Immunosuppression: Genetic Analysis of Noncoding Control Region (NCCR) Variability among a HIV-1-Positive Population. Viruses, 12.","DOI":"10.3390\/v12050507"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Prezioso, C., Bianchi, M., Obregon, F., Ciotti, M., Sarmati, L., Andreoni, M., Palamara, A.T., Pascarella, S., Moens, U., and Pietropaolo, V. (2020). Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21217998"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1093\/bib\/bbn017","article-title":"MEGA: A biologist-centric software for evolutionary analysis of DNA and protein sequences","volume":"9","author":"Kumar","year":"2008","journal-title":"Brief Bioinform."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1016\/j.humpath.2010.12.013","article-title":"Immunohistochemistry for Merkel cell polyomavirus is highly specific but not sensitive for the diagnosis of Merkel cell carcinoma in the Australian population","volume":"42","author":"Paik","year":"2011","journal-title":"Hum. Pathol."},{"key":"ref_20","first-page":"1057","article-title":"Detection of Merkel cell polyomavirus in formalin-fixed, paraffin-embedded tissue of Merkel cell carcinoma and correlation with prognosis","volume":"55","author":"Andea","year":"2014","journal-title":"Rom. J. Morphol. Embryol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ejca.2018.02.003","article-title":"The association between geographic location and incidence of Merkel cell carcinoma in comparison to melanoma: An international assessment","volume":"94","author":"Stang","year":"2018","journal-title":"Eur. J. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1097\/00000658-199901000-00013","article-title":"Surgical management of Merkel cell carcinoma","volume":"229","author":"Allen","year":"1999","journal-title":"Ann. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1093\/infdis\/jiy070","article-title":"Genetic variability of the noncoding control region of cutaneous Merkel cell polyomavirus: Identification of geographically related genotypes","volume":"217","author":"Hashida","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/jid.2008.198","article-title":"MC polyomavirus is frequently present in Merkel cell carcinoma of European patients","volume":"129","author":"Becker","year":"2009","journal-title":"J. Investig. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1002\/hed.22942","article-title":"Significant overexpression of the Merkel cell polyomavirus (MCPyV) large T antigen in Merkel cell carcinoma","volume":"35","author":"Erovic","year":"2013","journal-title":"Head Neck"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Haymerle, G., Janik, S., Fochtmann, A., Pammer, J., Schachner, H., Nemec, L., Mildner, M., Houben, R., Grasl, M.C., and Erovic, B.M. (2017). Expression of Merkelcell polyomavirus (MCPyV) large T-antigen in Merkel cell carcinoma lymph node metastases predicts poor outcome. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0180426"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/jid.2011.260","article-title":"Merkel cell carcinoma and Merkel cell polyomavirus: Evidence for hit-and-run oncogenesis","volume":"132","author":"Houben","year":"2012","journal-title":"J. Investig. Dermatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/apm.13019","article-title":"Merkel cell polyomavirus and non-Merkel cell carcinomas: Guilty or circumstantial evidence?","volume":"128","author":"Csoboz","year":"2020","journal-title":"APMIS"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/1\/61\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:07:06Z","timestamp":1760159226000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/1\/61"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,5]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["v13010061"],"URL":"https:\/\/doi.org\/10.3390\/v13010061","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2021,1,5]]}}}