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dc.contributor.authorMendoza, María Dolores
dc.contributor.authorSantonja, Carlos
dc.contributor.authorGonzález Vela, María del Carmen 
dc.contributor.authorConcha, Ángel
dc.contributor.authorIglesias Pena, Nicolás
dc.contributor.authorAndrés Esteban, Eva María
dc.contributor.authorVaqué Díez, José Pedro 
dc.contributor.authorCereceda, Laura
dc.contributor.authorPajares, Raquel
dc.contributor.authorKutzner, H.
dc.contributor.authorRequena, Luis
dc.contributor.authorPiris, Miguel A.
dc.contributor.otherUniversidad de Cantabriaes_ES
dc.date.accessioned2021-02-18T16:17:09Z
dc.date.available2021-02-18T16:17:09Z
dc.date.issued2020
dc.identifier.issn1932-6203
dc.identifier.otherSAF2013-47416-Res_ES
dc.identifier.urihttp://hdl.handle.net/10902/20729
dc.description.abstractAims: Merkel cell carcinoma (MCC) is an aggressive primary neuroendocrine tumor of the skin, associated with Merkel cell polyomavirus (MCPyV) in 49-89% of cases, depending on the country of origin and the techniques of detection. The presence of MCPyV defines heterogeneity in MCC; MCPyV-negative cases bear a much higher mutational load, with a distinct ultraviolet signature pattern featuring C > T transitions, as a consequence of exposure to ultraviolet light radiation. MCC stroma has not been thoroughly studied, although MCC patients benefit from therapy targeting PD1/PDL1. Methods and results: In this study, using Tissue Microarrays and immunohistochemistry, we have analyzed a series of 219 MCC cases in relation to the presence of MCPyV, and confirmed that the presence of MCPyV is associated with changes not only in the neoplastic cells, but also in the composition of the tumor stroma. Thus, MCPyV, found in 101/176 (57,4%) analyzable cases, exhibits changes in its tumor morphology, the density of the inflammatory infiltrate, the phenotype of the neoplastic cells, and the cell composition of the tumor stroma. MCPyV presence is negatively correlated with a higher level of p53 expression, and associated with a very high frequency (86%) of HLA-I expression loss, a higher apoptotic index, and a stroma richer in T-cells, cytotoxic T-cells, macrophages, PDL1-positive macrophages, and B-cells. Conclusions: Our findings provide evidence of the basic heterogeneity of MCC, supporting the hypothesis that the presence of MCPyV may induce a rich inflammatory response, which is at least partially avoided through loss of HLA-I antigen expression. On the other hand, MCPyV-negative cases show a much higher frequency of stronger p53 expression and, probably, p53 alterations.es_ES
dc.description.sponsorshipDr. Piris is the principal investigator of all the projects funding this study. This work was supported by grants from the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Economy and Competence (MINECO, RTICC ISCIII and CIBERONC) (SAF2013-47416-R, RD06/0020/0107-RD012/0036/0060 and Plan Nacional I+D+I: PI17/2172, PI16/01294 and PIE15/0081), AECC, and the Madrid Autonomous Community.es_ES
dc.format.extent12 p.es_ES
dc.language.isoenges_ES
dc.publisherPublic Library of Sciencees_ES
dc.rightsAttribution 4.0 Internationales_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.sourcePLoS One . 2020 Jul 20;15(7):e0232517es_ES
dc.titleThe presence of Merkel cell carcinoma polyomavirus is associated with a distinct phenotype in neoplastic Merkel cell carcinoma cells and their tissue microenvironmentes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.relation.publisherVersionhttps://doi.org/10.1371/journal.pone.0232517es_ES
dc.rights.accessRightsopenAccesses_ES
dc.identifier.DOI10.1371/journal.pone.0232517
dc.type.versionpublishedVersiones_ES


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Attribution 4.0 InternationalExcepto si se señala otra cosa, la licencia del ítem se describe como Attribution 4.0 International