Dataset Information

NTRK2 expression in gastrointestinal stromal tumors with a special emphasis on the clinicopathological and prognostic impacts.

ABSTRACT: Gastrointestinal stromal tumors (GISTs) are typically characterized by activating mutations of the KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor alpha (PDGFRA). Recently, the neurotrophic tyrosine receptor kinase (NTRK) fusion was reported in a small subset of wild-type GIST. We examined trk IHC and NTRK gene expressions in GIST. Pan-trk immunohistochemistry (IHC) was positive in 25 (all 16 duodenal and 9 out of 16 small intestinal GISTs) of 139 cases, and all pan-trk positive cases showed diffuse and strong expression of c-kit. Interestingly, all of these cases showed only trkB but not trkA/trkC expression. Cap analysis of gene expression (CAGE) analysis identified increased number of genes whose promoters were activated in pan-trk/trkB positive GISTs. Imbalanced expression of NTRK2, which suggests the presence of NTRK2 fusion, was not observed in any of trkB positive GISTs, despite higher mRNA expression. TrkB expression was found in duodenal GISTs and more than half of small intestinal GISTs, and this subset of cases showed poor prognosis. However, there was not clear difference in clinical outcomes according to the trkB expression status in small intestinal GISTs. These findings may provide a possible hypothesis for trkB overexpression contributing to the tumorigenesis and aggressive clinical outcome in GISTs of duodenal origin.

SUBMITTER: Sasa K

PROVIDER: S-EPMC10774370 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

NTRK2 expression in gastrointestinal stromal tumors with a special emphasis on the clinicopathological and prognostic impacts.

Sasa Keita K Son Raku R Oguchi Akiko A Ashizawa Karin K Hasegawa Nobuhiko N Kubota Daisuke D Suehara Yoshiyuki Y Takagi Tatsuya T Okubo Taketo T Akaike Keisuke K Sugimoto Kiichi K Takahashi Makoto M Sakamoto Kazuhiro K Hashimoto Takashi T Mine Shinji S Fukunaga Tetsu T Ishijima Muneaki M Hayashi Takuo T Yao Takashi T Murakawa Yasuhiro Y Saito Tsuyoshi T

Scientific reports 20240108 1

Gastrointestinal stromal tumors (GISTs) are typically characterized by activating mutations of the KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor alpha (PDGFRA). Recently, the neurotrophic tyrosine receptor kinase (NTRK) fusion was reported in a small subset of wild-type GIST. We examined trk IHC and NTRK gene expressions in GIST. Pan-trk immunohistochemistry (IHC) was positive in 25 (all 16 duodenal and 9 out of 16 small intestinal GISTs) of 139 cas ...[more]

PMID: 38191907

Similar Datasets

Project description:The objective of the study was to investigate whether special stains can differentiate gastrointestinal stromal tumors (GISTs) and gastrointestinal leiomyomas (GILs). In this retrospective study, 39 cases of GISTs (diameter, 0.2-8.8 cm) and 75 cases of GILs (diameter, 0.2-4.5 cm) were recruited, all biopsy specimens were obtained by endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) excision, and the depth of excision included the whole mucosa, mucosal myometria, and most submucosa. GISTs and GILs were the most common types of mesenchymal tumors found anywhere along the gastrointestinal (GI) tract, from the esophagus to the rectum. GISTs were often associated with a higher risk of malignancy. In this study, the gender, age of onset, size and sites of the lesions, together with the number of mucosal or lamina propria lesions all have significant differences, nevertheless, there was no significant difference in cell morphology of GISTs and GILs tested by hematoxylin eosin (H&E) stain, and all showed low echo areas by EUS examination. In this retrospective study, the GISTs and GILs had been diagnosed by immunohistochemistry combined with clinical morphology. Subsequently, special stains including Masson's trichrome (MT) stain, Alcian blue periodic acid-Schiff (AB-PAS) stain (pH 2.5), Wright-Giemsa (W-G) stain and periodic acid-Schiff (PAS) combined with diastase periodic acid-Schiff (D-PAS) stains were also applied in the diagnosis, the retrospective study results showed that 92.3% GISTs were stained blue with MT stain, 97.3% GILs were stained red with MT stain (P < 0.01), almost all GISTs were PAS-negative (light purple), in contrast, all GILs were PAS-positive (rose red) (P < 0.01), all of these experiments set control using the blood vessels stained by MT and AB-PAS stains. Nevertheless, there was no significant difference between GISTs and GILs stained by W-G stain. These obvious and meaningful differential results were also confirmed in the detection of new GISTs and GILs cases using MT and AB-PAS stains. In conclusion, MT and AB-PAS stains could also identify GISTs and GILs cases, particularly, AB-PAS was more sensitive and more specific, providing a more cost-effective, simple, and high sensitivity and specificity inspection methods, which should be noticed and widely used in the future, especially in resource-limited grass-roots testing institution or in cases with inconclusive immunostains or insufficient material.

Project description:BackgroundGastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Surgical resection and tyrosine kinase inhibitors are defined as the main treatments but cannot cure patients with advanced GIST, which eventually develops into recurrence and acquired drug resistance. Therefore, it is necessary to identify prognostic biomarkers and new therapeutic targets for GISTs. CC chemokine receptor type 8 (CCR8) protein participates in regulation of immune responses. Recent studies on CCR8 in non-small cell lung cancer and colorectal cancer showed that it was highly expressed in tumor-infiltrating regulatory T cells and correlated with a poor prognosis.AimTo detect CCR8 expression in GIST tissues and analyze its relationships with clinicopathological features and prognosis in patients with GISTs.MethodsTissue samples were used for the tissue microarrays construction. The microarrays were then subjected to immunohistochemical analyses to detect CCR8 expression. Next, Kaplan-Meier analysis was utilized to calculate the survival rate of patients with complete follow-up data, and the potential prognostic value of CCR8 was evaluated by Cox regression analysis. Finally, a Gene Ontology/Kyoto Encyclopedia of Genes and Genomes single-gene enrichment chart of CCR8 was constructed using the STRING database.ResultsCCR8-positive signals were detected as brown or brown-yellow particles by immunohistochemistry located in the cytoplasm. Among 125 tissue samples, 74 had CCR8 high expression and 51 had low or negative expression. Statistical analyses suggested CCR8 was significantly correlated with tumor size, mitotic index, AFIP-Miettinen risk classification and tumor location. Kaplan-Meier and multivariate analyses showed that patients with low or negative CCR8 expression, mitotic index < 5/high-power fields (HPF) and tumor diameter < 5 cm had a better prognosis. Based on the STRING database, CCR8 was significantly enriched in biological processes such as tumor immunity, T lymphocyte chemotaxis, migration and pathways like the nuclear factor-κB and tumor necrosis factor pathways as well as intestinal immune regulation networks.ConclusionCCR8 is a prognostic biomarker for malignant potential of GISTs, with high expression correlated with malignancy and poor prognosis.

Dataset Information

NTRK2 expression in gastrointestinal stromal tumors with a special emphasis on the clinicopathological and prognostic impacts.

Publications

NTRK2 expression in gastrointestinal stromal tumors with a special emphasis on the clinicopathological and prognostic impacts.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets