The prognostic role of PD-L1 expression and the presence of polyomavirus in Merkel cell carcinoma cases

Abstract Background Merkel cell carcinoma (MCC) comprises a rare malignant primary skin tumor presenting neuroendocrine differentiation. Recently, agents blocking the programmed cell death protein 1 and programmed cell death protein ligand 1 pathway (PD-1/PD-L1) have demonstrated objective and durab...

Full description

Bibliographic Details
Main Authors: Stella Meireles Siqueira, Gabriella Campos-do-Carmo, Paulo Ricardo Garcia da Silva, Isabele Ávila Small, Andreia Cristina De Melo
Format: Article
Language:English
Published: BMC 2024-01-01
Series:Infectious Agents and Cancer
Subjects:
Online Access:https://doi.org/10.1186/s13027-023-00564-1
_version_ 1827388743597686784
author Stella Meireles Siqueira
Gabriella Campos-do-Carmo
Paulo Ricardo Garcia da Silva
Isabele Ávila Small
Andreia Cristina De Melo
author_facet Stella Meireles Siqueira
Gabriella Campos-do-Carmo
Paulo Ricardo Garcia da Silva
Isabele Ávila Small
Andreia Cristina De Melo
author_sort Stella Meireles Siqueira
collection DOAJ
description Abstract Background Merkel cell carcinoma (MCC) comprises a rare malignant primary skin tumor presenting neuroendocrine differentiation. Recently, agents blocking the programmed cell death protein 1 and programmed cell death protein ligand 1 pathway (PD-1/PD-L1) have demonstrated objective and durable tumor regressions in patients presenting advanced MCC. This study aimed to describe the sociodemographic, clinical, and histopathological characteristics of MCC patients, also assessing the prevalence of PD-L1 expression and Merkel cell Polyomavirus (MCPyV), as well as their prognostic roles. Methods Data from patients diagnosed with MCC between 1996 and 2019 at a reference cancer center in Rio de Janeiro, southeastern Brazil, were evaluated in a retrospective study. Tumor samples were tested for MCPyV and PD-L1 employing immunohistochemistry. Survival analyses were carried out employing the Kaplan–Meier method and curves were compared using the log-rank test. A multiple semiparametric Cox model was used. Values p < 0.05 were considered significant. Results A total of 65 patients were included in the study, with a mean age at diagnosis of 72 (standard deviation 13.9). A total of 56.9% (37/65) of the patients were male, 86.2% (56/65) were white, and 56.9% (37/64) were illiterate or with incomplete elementary school. MCPyV immunohistochemistry was positive in 29 cases (44.6%) and PD-L1 positivity was ≥ 1% in 42 cases (64.6%). Significant associations between MCPyV and PD-L1 expression ≥ 1% (p = 0.003) and PD-L1 expression ≥ 5% (p = 0.005) were noted. Concerning the multivariate analysis, only education level and advanced MCC stage indicated statistically significant worse progression-free survival. Regarding overall survival (OS), being male, education level and advanced stage comprised risk factors. The estimated OS at 60 months for stages I to III was of 48.9% and for stage IV, 8.9%. Conclusions This is the first large Brazilian cohort to assess the prevalence of MCPyV in MCC tumors, as well as PD-L1 expression and their associations. No correlations were noted between MCPyV infection or PD-L1 expression and survival rates.
first_indexed 2024-03-08T16:23:21Z
format Article
id doaj.art-63bd7945162d438e85b4afcc8d2e289f
institution Directory Open Access Journal
issn 1750-9378
language English
last_indexed 2024-03-08T16:23:21Z
publishDate 2024-01-01
publisher BMC
record_format Article
series Infectious Agents and Cancer
spelling doaj.art-63bd7945162d438e85b4afcc8d2e289f2024-01-07T12:11:55ZengBMCInfectious Agents and Cancer1750-93782024-01-0119111010.1186/s13027-023-00564-1The prognostic role of PD-L1 expression and the presence of polyomavirus in Merkel cell carcinoma casesStella Meireles Siqueira0Gabriella Campos-do-Carmo1Paulo Ricardo Garcia da Silva2Isabele Ávila Small3Andreia Cristina De Melo4Division of Clinical Research and Technological Development, Brazilian National Cancer InstituteDermatology, Gávea Medical CenterDivision of Pathology, Brazilian National Cancer InstituteDivision of Clinical Research and Technological Development, Brazilian National Cancer InstituteDivision of Clinical Research and Technological Development, Brazilian National Cancer InstituteAbstract Background Merkel cell carcinoma (MCC) comprises a rare malignant primary skin tumor presenting neuroendocrine differentiation. Recently, agents blocking the programmed cell death protein 1 and programmed cell death protein ligand 1 pathway (PD-1/PD-L1) have demonstrated objective and durable tumor regressions in patients presenting advanced MCC. This study aimed to describe the sociodemographic, clinical, and histopathological characteristics of MCC patients, also assessing the prevalence of PD-L1 expression and Merkel cell Polyomavirus (MCPyV), as well as their prognostic roles. Methods Data from patients diagnosed with MCC between 1996 and 2019 at a reference cancer center in Rio de Janeiro, southeastern Brazil, were evaluated in a retrospective study. Tumor samples were tested for MCPyV and PD-L1 employing immunohistochemistry. Survival analyses were carried out employing the Kaplan–Meier method and curves were compared using the log-rank test. A multiple semiparametric Cox model was used. Values p < 0.05 were considered significant. Results A total of 65 patients were included in the study, with a mean age at diagnosis of 72 (standard deviation 13.9). A total of 56.9% (37/65) of the patients were male, 86.2% (56/65) were white, and 56.9% (37/64) were illiterate or with incomplete elementary school. MCPyV immunohistochemistry was positive in 29 cases (44.6%) and PD-L1 positivity was ≥ 1% in 42 cases (64.6%). Significant associations between MCPyV and PD-L1 expression ≥ 1% (p = 0.003) and PD-L1 expression ≥ 5% (p = 0.005) were noted. Concerning the multivariate analysis, only education level and advanced MCC stage indicated statistically significant worse progression-free survival. Regarding overall survival (OS), being male, education level and advanced stage comprised risk factors. The estimated OS at 60 months for stages I to III was of 48.9% and for stage IV, 8.9%. Conclusions This is the first large Brazilian cohort to assess the prevalence of MCPyV in MCC tumors, as well as PD-L1 expression and their associations. No correlations were noted between MCPyV infection or PD-L1 expression and survival rates.https://doi.org/10.1186/s13027-023-00564-1Merkel cell carcinomaMerkel cell polyomavirusProgrammed death ligand-1Skin cancer
spellingShingle Stella Meireles Siqueira
Gabriella Campos-do-Carmo
Paulo Ricardo Garcia da Silva
Isabele Ávila Small
Andreia Cristina De Melo
The prognostic role of PD-L1 expression and the presence of polyomavirus in Merkel cell carcinoma cases
Infectious Agents and Cancer
Merkel cell carcinoma
Merkel cell polyomavirus
Programmed death ligand-1
Skin cancer
title The prognostic role of PD-L1 expression and the presence of polyomavirus in Merkel cell carcinoma cases
title_full The prognostic role of PD-L1 expression and the presence of polyomavirus in Merkel cell carcinoma cases
title_fullStr The prognostic role of PD-L1 expression and the presence of polyomavirus in Merkel cell carcinoma cases
title_full_unstemmed The prognostic role of PD-L1 expression and the presence of polyomavirus in Merkel cell carcinoma cases
title_short The prognostic role of PD-L1 expression and the presence of polyomavirus in Merkel cell carcinoma cases
title_sort prognostic role of pd l1 expression and the presence of polyomavirus in merkel cell carcinoma cases
topic Merkel cell carcinoma
Merkel cell polyomavirus
Programmed death ligand-1
Skin cancer
url https://doi.org/10.1186/s13027-023-00564-1
work_keys_str_mv AT stellameirelessiqueira theprognosticroleofpdl1expressionandthepresenceofpolyomavirusinmerkelcellcarcinomacases
AT gabriellacamposdocarmo theprognosticroleofpdl1expressionandthepresenceofpolyomavirusinmerkelcellcarcinomacases
AT pauloricardogarciadasilva theprognosticroleofpdl1expressionandthepresenceofpolyomavirusinmerkelcellcarcinomacases
AT isabeleavilasmall theprognosticroleofpdl1expressionandthepresenceofpolyomavirusinmerkelcellcarcinomacases
AT andreiacristinademelo theprognosticroleofpdl1expressionandthepresenceofpolyomavirusinmerkelcellcarcinomacases
AT stellameirelessiqueira prognosticroleofpdl1expressionandthepresenceofpolyomavirusinmerkelcellcarcinomacases
AT gabriellacamposdocarmo prognosticroleofpdl1expressionandthepresenceofpolyomavirusinmerkelcellcarcinomacases
AT pauloricardogarciadasilva prognosticroleofpdl1expressionandthepresenceofpolyomavirusinmerkelcellcarcinomacases
AT isabeleavilasmall prognosticroleofpdl1expressionandthepresenceofpolyomavirusinmerkelcellcarcinomacases
AT andreiacristinademelo prognosticroleofpdl1expressionandthepresenceofpolyomavirusinmerkelcellcarcinomacases