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Combined Positive Score for Programmed Death Ligand-1 Expression and Inflammatory Microenvironment in Gastrointestinal Stromal Tumors

Background and Objectives: GISTs are the most frequent type of mesenchymal neoplasm of the digestive tract. The prognosis is mainly determined by tumor dimensions, mitotic rate and location, but other less well-documented factors can influence evolution and survival. The immune microenvironment and...

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Autores principales: Herlea, Vlad, Roșulescu, Alexandra, Calotă, Violeta Claudia, Croitoru, Vlad, Stoica Mustafa, Elena, Vasilescu, Cătălin, Alexandrescu, Sorin, Dumitrașcu, Traian, Popescu, Irinel, Dima, Simona Olimpia, Sajin, Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8924898/
https://www.ncbi.nlm.nih.gov/pubmed/35208498
http://dx.doi.org/10.3390/medicina58020174
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author Herlea, Vlad
Roșulescu, Alexandra
Calotă, Violeta Claudia
Croitoru, Vlad
Stoica Mustafa, Elena
Vasilescu, Cătălin
Alexandrescu, Sorin
Dumitrașcu, Traian
Popescu, Irinel
Dima, Simona Olimpia
Sajin, Maria
author_facet Herlea, Vlad
Roșulescu, Alexandra
Calotă, Violeta Claudia
Croitoru, Vlad
Stoica Mustafa, Elena
Vasilescu, Cătălin
Alexandrescu, Sorin
Dumitrașcu, Traian
Popescu, Irinel
Dima, Simona Olimpia
Sajin, Maria
author_sort Herlea, Vlad
collection PubMed
description Background and Objectives: GISTs are the most frequent type of mesenchymal neoplasm of the digestive tract. The prognosis is mainly determined by tumor dimensions, mitotic rate and location, but other less well-documented factors can influence evolution and survival. The immune microenvironment and checkpoint molecule expression were proven to impact the prognosis in different types of cancer. The aim of this study was to determine PD-L1 expression in GISTs and to evaluate the level of intratumoral immune infiltration in relation to prognostic variables and survival. Materials and Methods: Sixty-five GISTs diagnosed in the same institution between 2015 and 2018 were immunohistochemically tested for PD-L1 and evaluated using CPS. Immune cells were emphasized, with CD3, CD4, CD8, CD20 and CD68 antibodies and quantified. All data were processed using statistical tools. Results: The median age was 61 years (range, 28–78) and 36 patients (55.4%) were males. The location of the tumors was predominantly gastric (46%), followed by the small bowel (17%) and colorectal (6%). In addition, 11% were EGISTs and 20% were secondary tumors (11% metastases and 9% local recurrences). PD-L1 had a variable expression in tumor and inflammatory cells, with a CPS ranging from 0 to 100. Moreover, 64.6% of cases were PD-L1 positive with no significant differences among categories of variables, such as the age and the sex of the patient, tumor location, the primary or secondary character of the tumor, dimensions, mitotic rate, the risk of disease progression and tumor cell type. Immune cells had a variable distribution throughout the tumors. CD3+ lymphocytes were the most frequent type. CD20+ cells were identified in a larger number in tumors ≤5 cm (p = 0.038). PD-L1-positive tumors had a higher number of immune cells, particularly CD3+, CD20+ and CD68+, in comparison to PD-L1-negative ones (p = 0.032, p = 0.051, p = 0.008). Epithelioid and mixed cell-type tumors had a higher number of CD68+ cells. Survival was not influenced by PD-L1 expression; instead, it was decreased in multifocal tumors (p = 0.0001) and in cases with Ki67 ≥ 50% (p = 0.008). Conclusions: PD-L1-positive expression and the presence of different immune cell types, in variable quantities, can contribute to a better understanding of the complex interactions between tumor cells and the microenvironment, with a possible therapeutic role in GISTs.
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spelling pubmed-89248982022-03-17 Combined Positive Score for Programmed Death Ligand-1 Expression and Inflammatory Microenvironment in Gastrointestinal Stromal Tumors Herlea, Vlad Roșulescu, Alexandra Calotă, Violeta Claudia Croitoru, Vlad Stoica Mustafa, Elena Vasilescu, Cătălin Alexandrescu, Sorin Dumitrașcu, Traian Popescu, Irinel Dima, Simona Olimpia Sajin, Maria Medicina (Kaunas) Article Background and Objectives: GISTs are the most frequent type of mesenchymal neoplasm of the digestive tract. The prognosis is mainly determined by tumor dimensions, mitotic rate and location, but other less well-documented factors can influence evolution and survival. The immune microenvironment and checkpoint molecule expression were proven to impact the prognosis in different types of cancer. The aim of this study was to determine PD-L1 expression in GISTs and to evaluate the level of intratumoral immune infiltration in relation to prognostic variables and survival. Materials and Methods: Sixty-five GISTs diagnosed in the same institution between 2015 and 2018 were immunohistochemically tested for PD-L1 and evaluated using CPS. Immune cells were emphasized, with CD3, CD4, CD8, CD20 and CD68 antibodies and quantified. All data were processed using statistical tools. Results: The median age was 61 years (range, 28–78) and 36 patients (55.4%) were males. The location of the tumors was predominantly gastric (46%), followed by the small bowel (17%) and colorectal (6%). In addition, 11% were EGISTs and 20% were secondary tumors (11% metastases and 9% local recurrences). PD-L1 had a variable expression in tumor and inflammatory cells, with a CPS ranging from 0 to 100. Moreover, 64.6% of cases were PD-L1 positive with no significant differences among categories of variables, such as the age and the sex of the patient, tumor location, the primary or secondary character of the tumor, dimensions, mitotic rate, the risk of disease progression and tumor cell type. Immune cells had a variable distribution throughout the tumors. CD3+ lymphocytes were the most frequent type. CD20+ cells were identified in a larger number in tumors ≤5 cm (p = 0.038). PD-L1-positive tumors had a higher number of immune cells, particularly CD3+, CD20+ and CD68+, in comparison to PD-L1-negative ones (p = 0.032, p = 0.051, p = 0.008). Epithelioid and mixed cell-type tumors had a higher number of CD68+ cells. Survival was not influenced by PD-L1 expression; instead, it was decreased in multifocal tumors (p = 0.0001) and in cases with Ki67 ≥ 50% (p = 0.008). Conclusions: PD-L1-positive expression and the presence of different immune cell types, in variable quantities, can contribute to a better understanding of the complex interactions between tumor cells and the microenvironment, with a possible therapeutic role in GISTs. MDPI 2022-01-24 /pmc/articles/PMC8924898/ /pubmed/35208498 http://dx.doi.org/10.3390/medicina58020174 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Herlea, Vlad
Roșulescu, Alexandra
Calotă, Violeta Claudia
Croitoru, Vlad
Stoica Mustafa, Elena
Vasilescu, Cătălin
Alexandrescu, Sorin
Dumitrașcu, Traian
Popescu, Irinel
Dima, Simona Olimpia
Sajin, Maria
Combined Positive Score for Programmed Death Ligand-1 Expression and Inflammatory Microenvironment in Gastrointestinal Stromal Tumors
title Combined Positive Score for Programmed Death Ligand-1 Expression and Inflammatory Microenvironment in Gastrointestinal Stromal Tumors
title_full Combined Positive Score for Programmed Death Ligand-1 Expression and Inflammatory Microenvironment in Gastrointestinal Stromal Tumors
title_fullStr Combined Positive Score for Programmed Death Ligand-1 Expression and Inflammatory Microenvironment in Gastrointestinal Stromal Tumors
title_full_unstemmed Combined Positive Score for Programmed Death Ligand-1 Expression and Inflammatory Microenvironment in Gastrointestinal Stromal Tumors
title_short Combined Positive Score for Programmed Death Ligand-1 Expression and Inflammatory Microenvironment in Gastrointestinal Stromal Tumors
title_sort combined positive score for programmed death ligand-1 expression and inflammatory microenvironment in gastrointestinal stromal tumors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8924898/
https://www.ncbi.nlm.nih.gov/pubmed/35208498
http://dx.doi.org/10.3390/medicina58020174
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