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 Detalle_Publicacion

The presence of Merkel cell carcinoma polyomavirus is associated with a distinct phenotype in neoplastic Merkel cell carcinoma cells and their tissue microenvironment

Abstract: Aims: 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.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: PLoS One . 2020 Jul 20;15(7):e0232517

Editorial: Public Library of Science

 Año de publicación: 2020

Nº de páginas: 12

Tipo de publicación: Artículo de Revista

 DOI: 10.1371/journal.pone.0232517

ISSN: 1932-6203

Url de la publicación: https://doi.org/10.1371/journal.pone.0232517

Autores/as

MENDOZA, MARÍA DOLORES

SANTONJA, CARLOS

IGLESIAS PENA, NICOLÁS

ANDRÉS ESTEBAN, EVA MARÍA

CERECEDA, LAURA

PAJARES, RAQUEL

KUTZNER, H.

REQUENA, LUIS

PIRIS, MIGUEL A.