Combined Positive Score for Programmed Death Ligand-1 Expression and Inflammatory Microenvironment in Gastrointestinal Stromal Tumors
<i>Background and Objectives</i>: 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 mi...
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| Format: | Article |
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MDPI AG
2022-01-01
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| Series: | Medicina |
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| Online Access: | https://www.mdpi.com/1648-9144/58/2/174 |
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| author | Vlad Herlea Alexandra Roșulescu Violeta Claudia Calotă Vlad Croitoru Elena Stoica Mustafa Cătălin Vasilescu Sorin Alexandrescu Traian Dumitrașcu Irinel Popescu Simona Olimpia Dima Maria Sajin |
| author_facet | Vlad Herlea Alexandra Roșulescu Violeta Claudia Calotă Vlad Croitoru Elena Stoica Mustafa Cătălin Vasilescu Sorin Alexandrescu Traian Dumitrașcu Irinel Popescu Simona Olimpia Dima Maria Sajin |
| author_sort | Vlad Herlea |
| collection | DOAJ |
| description | <i>Background and Objectives</i>: 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. <i>Materials and Methods</i>: 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. <i>Results</i>: 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 (<i>p</i> = 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 (<i>p</i> = 0.032, <i>p</i> = 0.051, <i>p</i> = 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 (<i>p</i> = 0.0001) and in cases with Ki67 ≥ 50% (<i>p</i> = 0.008). <i>Conclusions</i>: 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. |
| first_indexed | 2024-03-09T21:29:35Z |
| format | Article |
| id | doaj.art-7b6abb653c8d48a38e839c9cc206cff1 |
| institution | Directory Open Access Journal |
| issn | 1010-660X 1648-9144 |
| language | English |
| last_indexed | 2024-03-09T21:29:35Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Medicina |
| spelling | doaj.art-7b6abb653c8d48a38e839c9cc206cff12023-11-23T20:59:09ZengMDPI AGMedicina1010-660X1648-91442022-01-0158217410.3390/medicina58020174Combined Positive Score for Programmed Death Ligand-1 Expression and Inflammatory Microenvironment in Gastrointestinal Stromal TumorsVlad Herlea0Alexandra Roșulescu1Violeta Claudia Calotă2Vlad Croitoru3Elena Stoica Mustafa4Cătălin Vasilescu5Sorin Alexandrescu6Traian Dumitrașcu7Irinel Popescu8Simona Olimpia Dima9Maria Sajin10Department of Pathology, Fundeni Clinical Institute, 022328 Bucharest, RomaniaDepartment of Pathology, Fundeni Clinical Institute, 022328 Bucharest, RomaniaNational Institute of Public Health, 050463 Bucharest, RomaniaDepartment of Oncology, Fundeni Clinical Institute, 022328 Bucharest, RomaniaDepartment of Pathology, Fundeni Clinical Institute, 022328 Bucharest, Romania“Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania“Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania“Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, RomaniaFaculty of Medicine, “Titu Maiorescu” University, 031593 Bucharest, RomaniaCenter of Excellence for Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania“Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania<i>Background and Objectives</i>: 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. <i>Materials and Methods</i>: 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. <i>Results</i>: 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 (<i>p</i> = 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 (<i>p</i> = 0.032, <i>p</i> = 0.051, <i>p</i> = 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 (<i>p</i> = 0.0001) and in cases with Ki67 ≥ 50% (<i>p</i> = 0.008). <i>Conclusions</i>: 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.https://www.mdpi.com/1648-9144/58/2/174gastrointestinal stromal tumorsPD-L1combined positive scoreimmune cells |
| spellingShingle | Vlad Herlea Alexandra Roșulescu Violeta Claudia Calotă Vlad Croitoru Elena Stoica Mustafa Cătălin Vasilescu Sorin Alexandrescu Traian Dumitrașcu Irinel Popescu Simona Olimpia Dima Maria Sajin Combined Positive Score for Programmed Death Ligand-1 Expression and Inflammatory Microenvironment in Gastrointestinal Stromal Tumors Medicina gastrointestinal stromal tumors PD-L1 combined positive score immune cells |
| 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 | gastrointestinal stromal tumors PD-L1 combined positive score immune cells |
| url | https://www.mdpi.com/1648-9144/58/2/174 |
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