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The prevalence and prognostic impact of tumor-infiltrating lymphocytes in uterine carcinosarcoma

OBJECTIVE: To examine the prevalence and prognostic role of tumor microenvironment (TME) markers in uterine carcinosarcoma (UCS) through immunohistochemical characterization. METHODS: The internal database of our institution was queried out for women with UCS who underwent surgery and thereafter pos...

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Autores principales: da Silva, Jesse Lopes, de Albuquerque, Lucas Zanetti, Rodrigues, Fabiana Resende, de Mesquita, Guilherme Gomes, Chaves, Cláudia Bessa Pereira, Bonamino, Martín Hernán, de Melo, Andreia Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650400/
https://www.ncbi.nlm.nih.gov/pubmed/34876047
http://dx.doi.org/10.1186/s12885-021-09026-6
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author da Silva, Jesse Lopes
de Albuquerque, Lucas Zanetti
Rodrigues, Fabiana Resende
de Mesquita, Guilherme Gomes
Chaves, Cláudia Bessa Pereira
Bonamino, Martín Hernán
de Melo, Andreia Cristina
author_facet da Silva, Jesse Lopes
de Albuquerque, Lucas Zanetti
Rodrigues, Fabiana Resende
de Mesquita, Guilherme Gomes
Chaves, Cláudia Bessa Pereira
Bonamino, Martín Hernán
de Melo, Andreia Cristina
author_sort da Silva, Jesse Lopes
collection PubMed
description OBJECTIVE: To examine the prevalence and prognostic role of tumor microenvironment (TME) markers in uterine carcinosarcoma (UCS) through immunohistochemical characterization. METHODS: The internal database of our institution was queried out for women with UCS who underwent surgery and thereafter postoperative chemotherapy with carboplatin and paclitaxel between January 2012 and December 2017. Tissue microarrays containing surgical samples of UCS from 57 women were assessed by immunohistochemistry for CD3, CD4, CD8, FOXP3, PD-1, PD-L1, and PD-L2. RESULTS: The mean age was 65.3 years (range, 49 to 79 years). For the epithelial component (E), CD3_E and CD4_E were highly expressed in 38 (66.7%) and in 40 (70.1%) patients, respectively, and were significantly associated with more advanced stages (p = 0.038 and p = 0.025, respectively). CD8_E was highly expressed in 42 (73.7%) patients, FOXP3_E 16 (28.1%), PD-1_E 35 (61.4%), PD-L1_E 27 (47.4%) and PD-L2_E 39 (68.4%). For the sarcomatous component (S), the prevalence of high expression was: CD3_S 6 (10.5%), CD4_S 20 (35.1%), CD8_S 44 (77.2%), FOXP3_S 8 (14%), PD-1_S 14 (24.6%), PD-L1_S 14 (24.6%) and PD-L2_S 8 (14%). By multivariate analysis, the CD8/FOXP3_S ratio (p = 0.026), CD4_E (p = 0.010), PD-L1_E (p = 0.013) and PD-L1_S (p = 0.008) markers significantly influenced progression-free survival. CD4/FOXP3_S ratio (p = 0.043), PD-1_E (p = 0.011), PD-L1_E (p = 0.036) and PD-L1_S (p = 0.028) had a significant association with overall survival. CONCLUSION: Some differences in UCS clinical outcomes may be due to the subtype of TILs and PD-1/PD-L1 axis immune checkpoint signaling. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-09026-6.
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spelling pubmed-86504002021-12-07 The prevalence and prognostic impact of tumor-infiltrating lymphocytes in uterine carcinosarcoma da Silva, Jesse Lopes de Albuquerque, Lucas Zanetti Rodrigues, Fabiana Resende de Mesquita, Guilherme Gomes Chaves, Cláudia Bessa Pereira Bonamino, Martín Hernán de Melo, Andreia Cristina BMC Cancer Research OBJECTIVE: To examine the prevalence and prognostic role of tumor microenvironment (TME) markers in uterine carcinosarcoma (UCS) through immunohistochemical characterization. METHODS: The internal database of our institution was queried out for women with UCS who underwent surgery and thereafter postoperative chemotherapy with carboplatin and paclitaxel between January 2012 and December 2017. Tissue microarrays containing surgical samples of UCS from 57 women were assessed by immunohistochemistry for CD3, CD4, CD8, FOXP3, PD-1, PD-L1, and PD-L2. RESULTS: The mean age was 65.3 years (range, 49 to 79 years). For the epithelial component (E), CD3_E and CD4_E were highly expressed in 38 (66.7%) and in 40 (70.1%) patients, respectively, and were significantly associated with more advanced stages (p = 0.038 and p = 0.025, respectively). CD8_E was highly expressed in 42 (73.7%) patients, FOXP3_E 16 (28.1%), PD-1_E 35 (61.4%), PD-L1_E 27 (47.4%) and PD-L2_E 39 (68.4%). For the sarcomatous component (S), the prevalence of high expression was: CD3_S 6 (10.5%), CD4_S 20 (35.1%), CD8_S 44 (77.2%), FOXP3_S 8 (14%), PD-1_S 14 (24.6%), PD-L1_S 14 (24.6%) and PD-L2_S 8 (14%). By multivariate analysis, the CD8/FOXP3_S ratio (p = 0.026), CD4_E (p = 0.010), PD-L1_E (p = 0.013) and PD-L1_S (p = 0.008) markers significantly influenced progression-free survival. CD4/FOXP3_S ratio (p = 0.043), PD-1_E (p = 0.011), PD-L1_E (p = 0.036) and PD-L1_S (p = 0.028) had a significant association with overall survival. CONCLUSION: Some differences in UCS clinical outcomes may be due to the subtype of TILs and PD-1/PD-L1 axis immune checkpoint signaling. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-09026-6. BioMed Central 2021-12-07 /pmc/articles/PMC8650400/ /pubmed/34876047 http://dx.doi.org/10.1186/s12885-021-09026-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
da Silva, Jesse Lopes
de Albuquerque, Lucas Zanetti
Rodrigues, Fabiana Resende
de Mesquita, Guilherme Gomes
Chaves, Cláudia Bessa Pereira
Bonamino, Martín Hernán
de Melo, Andreia Cristina
The prevalence and prognostic impact of tumor-infiltrating lymphocytes in uterine carcinosarcoma
title The prevalence and prognostic impact of tumor-infiltrating lymphocytes in uterine carcinosarcoma
title_full The prevalence and prognostic impact of tumor-infiltrating lymphocytes in uterine carcinosarcoma
title_fullStr The prevalence and prognostic impact of tumor-infiltrating lymphocytes in uterine carcinosarcoma
title_full_unstemmed The prevalence and prognostic impact of tumor-infiltrating lymphocytes in uterine carcinosarcoma
title_short The prevalence and prognostic impact of tumor-infiltrating lymphocytes in uterine carcinosarcoma
title_sort prevalence and prognostic impact of tumor-infiltrating lymphocytes in uterine carcinosarcoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650400/
https://www.ncbi.nlm.nih.gov/pubmed/34876047
http://dx.doi.org/10.1186/s12885-021-09026-6
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