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.

L'expression de PD-L1 et les cellules immunitaires dans les tumeurs stromales gastro-intestinalesIntroduction. Le micro-environnement tumoral et l'expression des molécules des check-point sur les cellules tumorales ont était prouvé d'apporter des effets sur le plan thérapeutique et pronostic dans certains types de cancer. L'évaluation de cellules immunitaires et l'expression de PD-L1 dans les tumeurs stromales gastro-intestinales (GIST) pourrait se rendre très utile dans la prise en charge d'une immunothérapie ciblé pour certains patients. L'objectif de cette étude était de déterminer l'expression de PD-L1 et d'analyser l'infiltrat inflammatoire intratumoral dans différentes catégories de GIST. Matériel et méthodes. Vingt-quatre cas de GIST confirmés par immunohistochimie ont été examinés au microscope et testés pour PD-L1, CD3 et CD20. Leur expression a été quantifiée et une analyse statistique a été effectuée pour rechercher des différences entre les sous-groupes.

Gastrointestinal stromal tumors (GISTs) are rare neoplasms, colorectal location being met in less than 5% of cases. Knowledge about this site related particularities are limited. The aim of this study is to present our experience with colorectal GISTs between 2005 and 2018 from the clinical, morphological, and immunohistochemical perspectives, with emphasis on prognostic factors. From a total of 203 gastrointestinal stromal tumors registered, 12 were colorectal (6%). The number of colonic tumors surpassed that of the rectum (9 : 3) and on the right side were registered more cases than on the left side (6/3). 9 were primary tumors and 3 were recurrences. Men and women were represented equally and the age range was between 22 and 76. Tumor dimensions varied between 0.5 and 14 cm. Microscopically, spindle cell type was dominant. Mitotic rate was variable between 1 and 115/50HPFs. Accordingly, for primary tumors progression risks were assigned (low risk: 2 cases, intermediate risk: 3 cases and high risk: 4 cases). All GISTs were CD117 and DOG1 positive. Four of the patients died of the disease.

Background: Most of the Gastrointestinal Stromal Tumors (GISTs) are determined by mutations in C-KIT or PDGFRA genes. Mutation type influences the clinical evolution and treatment response. Case reports: This study aims to present particular cases of GIST referred for molecular testing, diagnosed and treated in our institution. Results: We present three cases in which genetic testing was performed. The first patient was diagnosed in a short-time interval with two GISTs, a gastric and a jejunal one, both with low risk of recurrence. To establish the relationship between the two, molecular analysis was performed and the conclusion was that we were facing synchronous, sporadic GISTs, a very rare instance. The second case was a patient with liver metastases, 3 years earlier having been diagnosed with a high risk duodenal GIST. The genetic test revealed a mutational status conferring imatinib sensitivity and therefore imatinib was continued. The third case was a patient with an early recurrence in within less than a year after surgery for gastric GIST. Molecular testing identified a mutation associated with a bad clinical outcome. The patient died 2 years later from diagnosis by disease progression. Conclusion: Although rarely performed, genetic analysis provides useful information regarding the prognosis and the response to TKIs.