The prognostic significance of tumor-infiltrating lymphocytes, PD-L1, BRCA mutation status and tumor mutational burden in early-stage high-grade serous ovarian carcinoma. A study by the Spanish Group for Ovarian Cancer Research (GEICO)

Pizarro, David; Romero-Muñiz, Ignacio; Pérez-Mies, Belén; Redondo Sánchez, Andrés; Caniego-Casas, Tamara; Carretero-Barrio, Irene; Cristóbal, Eva; Gutiérrez-Pecharromán, Ana; Santaballa, Ana; D’Angelo, Emanuela; Hardisson Hernáez, David Alonso; Vieites, Begoña; Matías-Guiu, Xavier; Estévez, Purificación; Guerra, Eva; Prat, Jaime; Poveda, Andrés; López-Guerrero, José Antonio; Palacios, José

The prognostic significance of tumor-infiltrating lymphocytes, PD-L1, BRCA mutation status and tumor mutational burden in early-stage high-grade serous ovarian carcinoma. A study by the Spanish Group for Ovarian Cancer Research (GEICO)

Early stages are under-represented in studies on the molecular and immune features of high-grade serous ovarian carcinoma (HGSOC), and specific studies focused on early-stage HGSOC are required for a better prognostic stratification and to personalize chemotherapy. The aim of this study was to deter...

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Detalhes bibliográficos
Autores:	Pizarro, David, Romero-Muñiz, Ignacio, Pérez-Mies, Belén, Redondo Sánchez, Andrés, Caniego-Casas, Tamara, Carretero-Barrio, Irene, Cristóbal, Eva, Gutiérrez-Pecharromán, Ana, Santaballa, Ana, D’Angelo, Emanuela, Hardisson Hernáez, David Alonso, Vieites, Begoña, Matías-Guiu, Xavier, Estévez, Purificación, Guerra, Eva, Prat, Jaime, Poveda, Andrés, López-Guerrero, José Antonio, Palacios, José
Formato:	artículo
Fecha de publicación:	2023
País:	España
Recursos:	Universidad Autónoma de Madrid
Repositorio:	Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:	inglés
OAI Identifier:	oai:repositorio.uam.es:10486/708464
Acesso em linha:	http://hdl.handle.net/10486/708464 https://dx.doi.org/10.3390/ijms241311183
Access Level:	acceso abierto
Palavra-chave:	BRCA early stage high-grade serous ovarian carcinoma PD-L1 TMB Medicina

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spelling	The prognostic significance of tumor-infiltrating lymphocytes, PD-L1, BRCA mutation status and tumor mutational burden in early-stage high-grade serous ovarian carcinoma. A study by the Spanish Group for Ovarian Cancer Research (GEICO)Pizarro, DavidRomero-Muñiz, IgnacioPérez-Mies, BelénRedondo Sánchez, AndrésCaniego-Casas, TamaraCarretero-Barrio, IreneCristóbal, EvaGutiérrez-Pecharromán, AnaSantaballa, AnaD’Angelo, EmanuelaHardisson Hernáez, David AlonsoVieites, BegoñaMatías-Guiu, XavierEstévez, PurificaciónGuerra, EvaPrat, JaimePoveda, AndrésLópez-Guerrero, José AntonioPalacios, JoséBRCAearly stagehigh-grade serous ovarian carcinomaPD-L1TMBMedicinaEarly stages are under-represented in studies on the molecular and immune features of high-grade serous ovarian carcinoma (HGSOC), and specific studies focused on early-stage HGSOC are required for a better prognostic stratification and to personalize chemotherapy. The aim of this study was to determine the prognostic significance of CD8+ and CD4+ tumor-infiltrating lymphocytes (TILs), tumoral cell PD-L1 expression, BRCA mutational status and tumor mutation burden (TMB) in early-stage HGSOC. A retrospective study was performed on stage I and II HGSOC from the Molecular Reclassification of Early Stages of Ovarian Cancer (RECLAMO) cohort from the Spanish Group of Ovarian Cancer Research (GEICO). Centralized histological typing was performed based on morphological and immunohistochemical features. Intraepithelial (i) and stromal (s) CD8+ and CD4+ T cells and PD-L1 were evaluated on tissue microarrays by immunohistochemistry. BRCA1 and BRCA2 mutation status and TMB were analyzed in tumor DNA using next-generation sequencing. The study included 124 tumors. High iCD8+ (>20 TILs/core), low/intermediate CD4+ (<20 TILs/core) and high CD8+/CD4+ ratio (>35/core) were associated with favorable outcomes. Tumor cell PD-L1 expression (TPS ≥ 1) was present in only 8% of tumors. In total, 11 (16%) and 6 (9%) out of 69 HGSOC tested carried pathogenic or likely pathogenic BRCA1 or BRCA2 mutations, respectively. Median TMB of 40 tumors analyzed was 5.04 mutations/Mb and only 6 tumors had 10 or more mutations/Mb. BRCA status and TMB were not associated with TILs or prognosis. When compared with studies on advanced HGSOC, our results suggested that prognostic variables differed according to stage and that more studies focused on early stages of HGSOC are needed to better stratify these tumors: This work was supported by Instituto de Salud Carlos III (ISCIII) (grants PI19/01331, PI22/01892 and PMP22/00054); CIBERONC (grant CB16/12/00316); European Development Re gional Fund ‘A way to achieve Europe’ (FEDER), Spanish Group of Research in Ovarian Cancer (GEICO group); and by the Spanish Association Against Cancer Scientific Foundation (AECC).MDPIDepartamento de Anatomía PatológicaFacultad de Medicina20232023-07-06research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/708464https://dx.doi.org/10.3390/ijms241311183reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7084642026-06-23T12:46:27Z
dc.title.none.fl_str_mv	The prognostic significance of tumor-infiltrating lymphocytes, PD-L1, BRCA mutation status and tumor mutational burden in early-stage high-grade serous ovarian carcinoma. A study by the Spanish Group for Ovarian Cancer Research (GEICO)
title	The prognostic significance of tumor-infiltrating lymphocytes, PD-L1, BRCA mutation status and tumor mutational burden in early-stage high-grade serous ovarian carcinoma. A study by the Spanish Group for Ovarian Cancer Research (GEICO)
spellingShingle	The prognostic significance of tumor-infiltrating lymphocytes, PD-L1, BRCA mutation status and tumor mutational burden in early-stage high-grade serous ovarian carcinoma. A study by the Spanish Group for Ovarian Cancer Research (GEICO) Pizarro, David BRCA early stage high-grade serous ovarian carcinoma PD-L1 TMB Medicina
title_short	The prognostic significance of tumor-infiltrating lymphocytes, PD-L1, BRCA mutation status and tumor mutational burden in early-stage high-grade serous ovarian carcinoma. A study by the Spanish Group for Ovarian Cancer Research (GEICO)
title_full	The prognostic significance of tumor-infiltrating lymphocytes, PD-L1, BRCA mutation status and tumor mutational burden in early-stage high-grade serous ovarian carcinoma. A study by the Spanish Group for Ovarian Cancer Research (GEICO)
title_fullStr	The prognostic significance of tumor-infiltrating lymphocytes, PD-L1, BRCA mutation status and tumor mutational burden in early-stage high-grade serous ovarian carcinoma. A study by the Spanish Group for Ovarian Cancer Research (GEICO)
title_full_unstemmed	The prognostic significance of tumor-infiltrating lymphocytes, PD-L1, BRCA mutation status and tumor mutational burden in early-stage high-grade serous ovarian carcinoma. A study by the Spanish Group for Ovarian Cancer Research (GEICO)
title_sort	The prognostic significance of tumor-infiltrating lymphocytes, PD-L1, BRCA mutation status and tumor mutational burden in early-stage high-grade serous ovarian carcinoma. A study by the Spanish Group for Ovarian Cancer Research (GEICO)
dc.creator.none.fl_str_mv	Pizarro, David Romero-Muñiz, Ignacio Pérez-Mies, Belén Redondo Sánchez, Andrés Caniego-Casas, Tamara Carretero-Barrio, Irene Cristóbal, Eva Gutiérrez-Pecharromán, Ana Santaballa, Ana D’Angelo, Emanuela Hardisson Hernáez, David Alonso Vieites, Begoña Matías-Guiu, Xavier Estévez, Purificación Guerra, Eva Prat, Jaime Poveda, Andrés López-Guerrero, José Antonio Palacios, José
author	Pizarro, David
author_facet	Pizarro, David Romero-Muñiz, Ignacio Pérez-Mies, Belén Redondo Sánchez, Andrés Caniego-Casas, Tamara Carretero-Barrio, Irene Cristóbal, Eva Gutiérrez-Pecharromán, Ana Santaballa, Ana D’Angelo, Emanuela Hardisson Hernáez, David Alonso Vieites, Begoña Matías-Guiu, Xavier Estévez, Purificación Guerra, Eva Prat, Jaime Poveda, Andrés López-Guerrero, José Antonio Palacios, José
author_role	author
author2	Romero-Muñiz, Ignacio Pérez-Mies, Belén Redondo Sánchez, Andrés Caniego-Casas, Tamara Carretero-Barrio, Irene Cristóbal, Eva Gutiérrez-Pecharromán, Ana Santaballa, Ana D’Angelo, Emanuela Hardisson Hernáez, David Alonso Vieites, Begoña Matías-Guiu, Xavier Estévez, Purificación Guerra, Eva Prat, Jaime Poveda, Andrés López-Guerrero, José Antonio Palacios, José
author2_role	author author author author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Departamento de Anatomía Patológica Facultad de Medicina
dc.subject.none.fl_str_mv	BRCA early stage high-grade serous ovarian carcinoma PD-L1 TMB Medicina
topic	BRCA early stage high-grade serous ovarian carcinoma PD-L1 TMB Medicina
description	Early stages are under-represented in studies on the molecular and immune features of high-grade serous ovarian carcinoma (HGSOC), and specific studies focused on early-stage HGSOC are required for a better prognostic stratification and to personalize chemotherapy. The aim of this study was to determine the prognostic significance of CD8+ and CD4+ tumor-infiltrating lymphocytes (TILs), tumoral cell PD-L1 expression, BRCA mutational status and tumor mutation burden (TMB) in early-stage HGSOC. A retrospective study was performed on stage I and II HGSOC from the Molecular Reclassification of Early Stages of Ovarian Cancer (RECLAMO) cohort from the Spanish Group of Ovarian Cancer Research (GEICO). Centralized histological typing was performed based on morphological and immunohistochemical features. Intraepithelial (i) and stromal (s) CD8+ and CD4+ T cells and PD-L1 were evaluated on tissue microarrays by immunohistochemistry. BRCA1 and BRCA2 mutation status and TMB were analyzed in tumor DNA using next-generation sequencing. The study included 124 tumors. High iCD8+ (>20 TILs/core), low/intermediate CD4+ (<20 TILs/core) and high CD8+/CD4+ ratio (>35/core) were associated with favorable outcomes. Tumor cell PD-L1 expression (TPS ≥ 1) was present in only 8% of tumors. In total, 11 (16%) and 6 (9%) out of 69 HGSOC tested carried pathogenic or likely pathogenic BRCA1 or BRCA2 mutations, respectively. Median TMB of 40 tumors analyzed was 5.04 mutations/Mb and only 6 tumors had 10 or more mutations/Mb. BRCA status and TMB were not associated with TILs or prognosis. When compared with studies on advanced HGSOC, our results suggested that prognostic variables differed according to stage and that more studies focused on early stages of HGSOC are needed to better stratify these tumors
publishDate	2023
dc.date.none.fl_str_mv	2023 2023-07-06
dc.type.none.fl_str_mv	research article http://purl.org/coar/resource_type/c_2df8fbb1 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	http://hdl.handle.net/10486/708464 https://dx.doi.org/10.3390/ijms241311183
url	http://hdl.handle.net/10486/708464 https://dx.doi.org/10.3390/ijms241311183
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	MDPI
publisher.none.fl_str_mv	MDPI
dc.source.none.fl_str_mv	reponame:Biblos-e Archivo. Repositorio Institucional de la UAM instname:Universidad Autónoma de Madrid
instname_str	Universidad Autónoma de Madrid
reponame_str	Biblos-e Archivo. Repositorio Institucional de la UAM
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The prognostic significance of tumor-infiltrating lymphocytes, PD-L1, BRCA mutation status and tumor mutational burden in early-stage high-grade serous ovarian carcinoma. A study by the Spanish Group for Ovarian Cancer Research (GEICO)

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