Features Of Gastrointestinal Stromal Tumors Research Articles

Genomic and clinical characterization of a familial GIST kindred intolerant to imatinib

Familial gastrointestinal stromal tumors (GIST) are rare. We present a kindred with multiple family members affected with multifocal GIST who underwent whole genome sequencing of the germline and tumor. Affected individuals with GIST harbored a germline variant found within exon 13 of the KIT gene (c.1965T>G; p.Asn655Lys, p.N655K) and a variant in the MSR1 gene (c.877 C > T; p.Arg293*, pR293X). Multifocal GISTs in the proband and her mother were treated with preoperative imatinib, which resulted in severe intolerance. The clinical features of multifocal GIST, cutaneous mastocytosis, allergies, and gut motility disorders seen in the affected individuals may represent manifestations of the multifunctional roles of KIT in interstitial cells of Cajal or mast cells and/or may be suggestive of additional molecular pathways which can contribute to tumorigenesis.

Endoscopic Characteristics of Small-Bowel Gastrointestinal Stromal Tumors Detected During Single-Balloon Enteroscopy: A Retrospective Analysis.

The endoscopic features of small-bowel gastrointestinal stromal tumors (GISTs) are not well defined. The objective of this study was to describe the endoscopic features of GISTs of the small intestine detected via single-balloon enteroscopy (SBE). Patients with surgically confirmed small intestinal GISTs from January 2014 to September 2022 were retrospectively analyzed. The hospital's electronic medical record system was used to retrieve the patients' data, including their demographics, clinical symptoms, hemoglobin on admission, endoscopic and computerized tomography findings, clinicopathological findings, and surgical management data. In total, 46 GIST patients (23 men and 23 women) with overt bleeding were included, with a mean age of 52 years (23-80 years). The typical duration of the symptoms was 48 hours. Four patients (8.70%) had lesions in the duodenum, 32 (69.56%) had lesions in the jejunum, 8 (17.39%) had lesions in the ileum, and 2 (4.35%) had lesions around the junction of the jejunum and ileum. Out of the 46 patients, 27 underwent SBE, and GISTs were visualized in 25, while the lesions could not be visualized in the remaining 2. Submucosal round (n = 13), submucosal sessile (n = 8), and invasive/penetrating (n = 4) were among the endoscopic tumor features. Twenty patients exhibited submucosal protuberant lesions, with ulceration, vascular nodules/congestion, or erosion on the surface, and 5 patients presented ulcerative infiltrative lesions. The multiple logistic regression analysis indicated that the invasive/penetrating characteristics of GISTs under SBE evaluation are significantly correlated with the risk level of GIST malignancy (P < .05). A variety of endoscopic characteristics could be observed during the preoperative SBE evaluation of small-intestine GISTs.

Characteristics of gastrointestinal stromal tumors associated to other tumors: Características de los tumores del estroma gastrointestinal asociados a otras neoplasias.

IntroductionOur aim is to analyze the differences between sporadic gastrointestinal stromal tumors and those associated with other tumors. MethodsRetrospective cohort study including patients with diagnosis of gastrointestinal stromal tumors operated at our center. Patients were divided into two groups, according to whether or not they had associated other tumors, both synchronously and metachronously. Disease free survival and overall survival were calculated for both groups. Results96 patients were included, 60 (62.5%) were male, with a median age of 66.8 (35–84). An association with other tumors was found in 33 cases (34.3%); 12 were synchronous (36.3%) and 21 metachronous (63.7%). The presence of mutations in associated tumors was 70% and in non-associated tumors 75%. Associated tumors were classified as low risk tumors based on Fletcher’s stratification scale (p = 0.001) as they usually were smaller in size and had less than ≤5 mitosis per 50 HPF compared to non-associated tumors. When analyzing overall survival, there were statistically significant differences (p = 0,035) between both groups. ConclusionThe relatively high proportion of gastrointestinal stromal tumors cases with associated tumors suggests the need to carry out a study to rule out presence of a second neoplasm and a long-term follow-up should be carried out in order to diagnose a possible second neoplasm. Gastrointestinal stromal tumors associated with other tumors have usually low risk of recurrence with a good long-term prognosis.

Capsule endoscopy in the diagnosis of exophytic gastrointestinal stromal tumor of the small intestine

The frequency of gastrointestinal stromal tumors (GISTs) is 0.1–0.3% of all neoplasms in the gastrointestinal tract. The most common clinical feature of GISTs is gastrointestinal bleeding caused by ulceration of the tumor. Based on a clinical case, the eff ectiveness of capsule endoscopy in diagnosing GISTs is demonstrated.

A Rare Case of Epithelioid Variant of Duodenal Gastrointestinal Tumour

Gastrointestinal stromal tumours (GISTs) are uncommon mesenchymal neoplasms of the digestive tract that develop from pluripotent mesenchymal stem cells. GISTs develop from interstitial cells of Cajal or their precursors that are distributed throughout the muscular wall of the gastrointestinal tract.&#x0D; Rare mesenchymal neoplasms of the gastrointestinal tract called gastrointestinal stromal tumours (GISTs) are derived from pluripotent mesenchymal stem cells. The interstitial cells of Cajal or their progenitors, which are dispersed throughout the muscular wall of the gastrointestinal system, give rise to gastrointestinal stromal tumours (GISTs). At a median age of 55–60 years old, they have an incidence of 10–20/million each year.[1-4] They develop mostly in the stomach (60%) and small intestine (35%) before developing in the rectum, oesophagus, omentum, and mesentery more than 5%. [2] Only less than 5% of GISTs are duodenal.[5] The majority of cases are sporadic, however 5% involve a family condition, such as neurofibromatosis type 1 or the Carney triad.[2] As a result of blockage, anaemia, or gastrointestinal bleeding from a core ulceration, they typically manifest with abdominal discomfort. The discovery of small duodenal GISTs during gastroscopy is possible.&#x0D; Within the GIST category, the epithelioid variant represents a distinct subtype that is less common than other variants, such as spindle cell or mixed cell types. The overall prevalence of epithelioid GISTs is relatively low compared to other subtypes. Large extragastric components may extend intraluminally or to the serosal side in larger tumours. GISTs have non-specific abdominal pain and distention as their clinical signs and symptoms; as a result, diagnosis and treatment are frequently delayed, which result in therapeutic failures and high morbidity and fatality rates. GISTs can exhibit a variety of histological subtypes under a microscope, including the spindle cell type (70%) and the epithelioid type (20–25%), as well as the combined spindle cell and epithelioid type. [6] The histopathological features of epithelioid GISTs have been extensively studied in the literature. One study by Pai et al. (2016) found that epithelioid GISTs had higher cellularity, higher mitotic counts, and more prominent nucleoli than other GIST subtypes. [7] Cytologically, the features of duodenal GIST resemble those of adenocarcinoma. Epithelioid Duodenal GIST must be differentiated from adenocarcinoma.&#x0D; We are reporting the case of a 68-year-old female who complained of pain abdomen, and constipation since 1 year. Pain was associated with nausea, vomiting, not able to digest food solid&gt;liquid and USG guided FNAC was advised. Cytological features confirmed the diagnosis of epithelioid variant of duodenal GIST.

Proteomic Characterization Identifies Clinically Relevant Subgroups of Gastrointestinal Stromal Tumors

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract, and it has high metastatic and recurrence rates. We aimed to characterize the proteomic features of GIST to understand biological processes and treatment vulnerabilities. Quantitative proteomics and phosphoproteomics analyses were performed on 193 patients with GIST to reveal the biological characteristics of GIST. Data-driven hypotheses were tested by performing functional experiments using both GIST cell lines and xenograft mouse models. Proteomic analysis revealed differences in the molecular features of GISTs from different locations or with different histological grades. MAPK7 was identified and functionally proved to be associated with tumor cell proliferation in GIST. Integrative analysis revealed that increased SQSTM1 expression inhibited the patient response to imatinib mesylate. Proteomics subtyping identified 4 clusters of tumors with different clinical and molecular attributes. Functional experiments confirmed the role of SRSF3 in promoting tumor cell proliferation and leading to poor prognosis. Our study provides a valuable data resource and highlights potential therapeutic approaches for GIST.

Clinical characteristics of gastrointestinal stromal tumors with lymph node metastasis: A retrospective single-centre case-controlled study.

e23509 Background: Lymph node metastasis of gastrointestinal stromal tumors (GISTs) rarely occurs, and lymphadenectomy is not routinely performed in GIST resection. To date, the relevant characteristics and prognosis of GIST patients with lymph node metastasis are not well known. Methods: From January 2010 to December 2021, GIST patients who underwent lymph node resection were enrolled in this study from a GIST referral centre. All patients were divided into either the LN- group (GISTs without lymph node metastasis) or the LN+ group (GISTs with lymph node metastasis). The clinicopathological features and follow-up data were analysed, and propensity score matching (PSM) was conducted to reduce bias caused by confounders. Results: Out of 1024 surgical patients, 198 patients (age, 52.23±13.54 years; 56.6% males) underwent GIST resection with lymph node dissection for lymphadenopathy, and 17 patients had lymph node metastases (17/1024, 1.66%; 17/198, 8.59%). The LN+ group had a higher mitotic count (P = 0.012) and a higher proportion of distant metastasis (P &lt; 0.001) than the LN- group. After PSM, 28 patients were included (18 in the LN- group and 10 in the LN+ group). The LN- group had both longer postoperative progression-free survival (PFS, not reached vs. 15.0 months, P = 0.002) and overall survival (OS) than the LN+ group, but the difference in OS was not statistically significant (not reached vs. 35.0 months, P = 0.069). Conclusions: The rate of lymph node metastasis in GISTs is low. Lymph node metastasis may be a less common form of distant metastasis. Moreover, GIST with lymph node metastasis has an unfavourable prognosis. Further studies are warranted to identify GISTs with lymph node involvement and the potential involved mechanism. [Table: see text]

Fluorine-18 fluorodeoxyglucose (18FDG)-uptake assessment of PDGFRA mutant gastrointestinal stromal tumors (GIST): A retrospective multicenter Italian study.

11539 Background: D842V PDGFRA mutation identifies a molecular subtype of GIST, primarly resistant to imatinib and characterized by higher indolent behavior and a prominent immune profile. Although functional imaging with 18FDG-PET plays a proven role in GIST, especially in early assessment tumor response, less is known about 18FDG-uptake according to the GIST molecular subtypes. Taking into account of clinical and molecular features of D842V mutant GIST, we assumed that this subset of GIST could also have a different 18FDG-uptake. Therefore, the aim of the present study has been to investigate the degree of FDG uptake of PDGFRA mutant GIST, focusing on D842V ones, in order to better define the role of functional imaging in this rare and peculiar subset of GIST. Methods: Patients with PDGFRA mutant GIST underwent 18FDG-PET were retrospectively included from seven GIST Italian reference centers. Data on maximum standardized uptake (SUVmax) value of primary tumor or metastatic disease were collected. Results: 71 patients have been included: 37 (55.1%) with D842V PDGFRA mutant GIST (group A) and 34 (47.9%) with PDGFRA non-D842V mutant GIST (group B). Additionally, 30 patients with exon 11 KIT mutant GIST have been included, as control (group C). SUVmax values were obtained from primary tumor and metastatic lesions in 55 (54,4%) and 46 (45,6%) patients, respectively. Considering the whole population of 101 patients, the global median SUVmax was 3,7 (IQR 0-9.1), while the median SUVmax for group A, B, and C was 0, 3.6, and 10.4, respectively. The median SUVmax of PDGFRA mutant GIST was significantly lower than the median value of exon 11 KIT mutant GIST (p &lt; 0.001). Notably, median 18FDG-uptake was significantly lower in D842V PDGFRA mutant GIST compared to PDGFRA non-D842V mutant ones (p = 0.021). Conclusions: PDGFRA D842V-mutant GIST present an overall lower 18FDG uptake compared to other GIST subgroups. This feature could be related to their specific molecular background and is consistent with their higher tendency to an indolent behavior. Therefore, the role of functional imaging with 18FDG-PET in this subset of GIST is limited. Finally, the prognostic value of the 18FDG-uptake degree within all PDGFRA mutant GIST will be investigated in the future.

Comprehensive genomic and transcriptomic profiling analysis of the recurrent gastrointestinal stromal tumor (GIST).

e23506 Background: The gastrointestinal stromal tumor (GIST) is a potentially malignant mesenchymal tumor (sarcoma), whose management has been transformed by approvals of TKIs. However, recurrence or metastasis is a formidable challenge in managing high-risk GIST. Comprehensive investigation of the transcriptome and genome in GIST is helpful to determine the therapy strategy for patients. This study aims to explore the molecular features of high-risk recurrence GIST. Methods: The tumor tissue samples of 42 patients with primary GIST were collected, in which all patients were divided into low-risk (n = 12), intermediate-risk (n = 11), and high-risk (n = 19) groups according to the NIH 2017th, in which 8 developed recurrence within three years and 11 without recurrence over three years in the high-risk group. Tumor-normal whole-exome and tumor mRNA sequencing was performed on baseline tissue DNA isolated from all patients. Results: Consistent with prior knowledge, KIT was the predominant mutation. The top mutated genes in GISTs were KIT (82%), PHLDA1 (39%), MUC6 (22%), ARID1B(20%), SURF2(20%), MGA(16%), MUC17(16%), MPRIP(16%) and PDGFRA(16%), which MUC6 was a significantly different mutation gene (DMG) associated with disease progression in terms of either high-risk(p = 0.04), recurrence(p = 0.02) or progression(p = 0.05). Interestingly, PDGFRA mutation co-occurs with CTNND2(p &lt; 0.01) and its correlated genes. Additionally, we further explored the somatic copy number variations (CNVs). amp_RAD51B(49%), amp_MLH3(41%), amp_CHEK2(37%), and amp_RB1(12%) seemed to be more frequent in the recurrence group, while these observations were not significant (p &gt; 0.05). Notably, del_NCOR1 or amp_NCOR1 was uniquely observed in the recurrence group. Compared with non-recurrence GIST, gene expression profiles revealed that mast cell activate (MCA)，M1-macrophages infiltration were higher in recurrence group, and mRNA was significantly upregulated in Systemic lupus erythematosus、Neutrophil extracellular trap formation、Viral carcinogenesis、Endocytosis. These pathways were indentified as being associated with recurrence and progression in other cancer studies. For example, the endocytosis pathway expression is positively associated with oncogenic pathway signaling in CRC, and neutrophil extracellular trap on cancer cells promotes liver metastasis in the tumor microenvironment. In the other, NCOR1 is a crucial regulator of T cell and B cell development. Conclusions: Here, we demonstrated the DNA/RNA profiles of GISTs. We observed higher CNVs in high-risk GIST. Especially, the high-risk recurred tumor presented different CNVs frequency and microenvironment. These results may contribute to understanding the mechanism of recurrence and improving recurrence detection.

Incidence Trends and Main Features of Gastro-Intestinal Stromal Tumours in a Mediterranean Region: A Population-Based Study.

Gastro-Intestinal Stromal Tumours (GISTs) are a kind of neoplasm whose diagnosis in common clinical practice just started in the current century, implying difficulties for proper registration. Staff from the Cancer Registry of Murcia, in southeastern Spain, were commissioned by the EU Joint Action on Rare Cancers into a pilot study addressing GIST registration that also yielded a population-based depiction of GISTs in the region, including survival figures. We examined reports from 2001 to 2015 from hospitals as well as cases already present in the registry. The variables collected were sex, date of diagnosis, age, vital status, primary location, presence of metastases, and risk level according to Joensuu's Classification. In total, 171 cases were found, 54.4% occurred in males, and the mean age value was 65.0 years. The most affected organ was the stomach, with 52.6% of cases. Risk level was determined as "High" for 45.0%, with an increment of lower levels in recent years. Incidence for the year 2015 doubled that of 2001. Overall, the 5-year net survival estimation was 77.0%. The rising incidence magnitude is consistent with trends in other European countries. Survival evolution lacked statistical significance. A more interventional approach in clinical management could explain the increase in the proportion of "Low Risk GISTs" and the first occurrence of "Very Low Risk" in recent years.

The relationship between Ki-67 expression and imaging signs and pathological features in GISTs.

To investigate the correlations between the Ki-67 index and plain-scan computerized tomography (CT) signs and pathological features of gastrointestinal stromal tumor (GIST) tissue. Data from 186 patients with GIST diagnosed by pathology and immunohistochemistry (IHC) in Peking University First Hospital from May 2016 to May 2022 were analyzed. The patients were divided into two groups: Ki-67 ≤5% and >5%. Correlation analysis, univariate and multivariate Logistic regression analysis were used to explore the correlations between CT signs, pathological features, and Ki-67 expression. Univariate indicators correlated with the Ki-67 index were mitotic count, pathological grade, tumor hemorrhage, tumor necrosis, tumor size, and tumor density. Multivariate Logistic regression indicated that the mitotic count [odds ratio (OR) 10.222, 95% confidence interval (CI) 4.312-31.039], pathological grade (OR 2.139, 95% CI 1.397-3.350), and tumor size (OR 1.096, 95% CI 1.020-1.190) were independently associated with the Ki-67 expression level. The concordance indexes (C-index) for the pathological features and CT signs models were 0.876 (95% CI 0.822-0.929) and 0.697 (95% CI 0.620-0.774), respectively, with positive predictive values of 93.62% and 58.11% and negative predictive values of 81.29% and 75.89%, respectively. After internal verification by the Bootstrap method, the fitting degree of the pathological features model was found to be better than that of the CT signs model. Mitotic count, pathological risk grading, and tumor size are independent risk factors correlating with high Ki-67 index. These results indicate that the Ki-67 index reflects tumor malignancy and can predict recurrence and metastasis of GIST.

Relationship between computed tomography and histological features of gastrointestinal stromal tumors

Background and Aim: Histomorphological and immunohistochemical (IHC) properties of gastrointestinal stromal tumors (GISTs) allow for accurate diagnosis and determine the prognosis. We aimed to evaluate the relationship between the computed tomography (CT) features, histomorphological properties, and IHC markers. Materials and Methods: This retrospective study comprised patients with pathologically confirmed GISTs between 2016 and 2021. The predefined CT characteristics comprised tumor size, hemorrhage and calcification, CT-growth pattern (exophytic/endophytic), and contrast enhancement pattern of the solid component (homogeneous/heterogeneous). The GISTs were divided into groups according to the National Institutes of Health risk category, cell type, presence of necrosis, CD117 and α-SMA positivity, and Ki-67 index. The frequencies of CT phenotypes were compared between groups. Results: Overall 24 (14 [58.3%] males) patients with a median age of 64 (59.5–75.5) having 25 GISTs were included. Of 25 GISTs, 16 (64%) were gastric and 9 (36%) were intestinal in origin. Among CT features, the maximum diameter was higher in epithelioid, infiltrative, a mitotic count ≥5/50, necrotic, high-risk GISTs (P &lt; 0.05 for all). The median tumor size was higher in Ki-67 &gt;8 than Ki-67 &lt;6 subjects (112.5 [39.25–153.75] vs. 22.5 [16.75–57.5] mm, P = 0.014). A heterogeneous enhancement was also more frequent in Ki-67 &gt;8 tumors (P = 0.04). The enhancement pattern did not differ according to CD-117 or SMA positivity. Logistic regression analysis revealed that the only independent predictor of a Ki-67 &gt;8 status was the tumor size (odds ratio: 1.02, 95% confidence interval: 1.001–1.046, P = 0.04). Conclusions: Heterogeneously enhanced large GISTs at CT imaging strongly suggest the presence of poor prognostic factors including a high Ki-67 index and/or high-risk category.

Expression of DOG 1 and correlation with Ki-67 and tumor characteristics in GIST: case series analysis in a tertiary care center

Gastrointestinal stromal tumours (GISTs) are the most common non epithelial, mesenchymal tumours of the gastrointestinal tract and amount to 1 to 3% of all gastrointestinal tumours. Histologically, GISTs demonstrate considerable morphologic variation. The aim of the study was to evaluate the histo-morphological features of GIST and the expression of DOG1 and KI-67 in these tumours. Eleven cases of GISTs received during a five-year period at a tertiary care centre were analysed for their demographic parameters, morphology and risk stratification. Immunohistochemistry for DOG1 and Ki67 was performed for all the eleven cases. In this study there was a female preponderance with the mid -fifties being the median age of presentation. The stomach and small intestine were the common sites of involvement. The histologic type was predominantly spindle cell with a few cases of mixed tumours. DOG 1 was positive in all the tumours and Ki-67 index was markedly elevated in the epithelioid cell type and in the high-risk category of tumours. DOG 1 holds good as an important marker for clinically suspected GIST diagnosis and Ki-67 expression correlates with the risk stratification of the tumour and can be a good prognostic factor.

SDH-deficient gastrointestinal stromal tumours

Gastrointestinal stromal tumours (GIST) comprise a heterogeneous group of the most common mesenchymal neoplasms of the gastrointestinal tract. The majority of GIST are induced by activating, mutually exclusive mutations of two genes – KIT and PDGFRA (platelet-derived growth factor receptor-alpha). However, approximately 10–15% of GISTs lack oncogenic KIT or PDGFRA mutations and these tumours are often called “wild type” (WT) GISTs. The SDH-deficient GISTs form a distinctive subset of tumours accounting for 20–40% of KIT/PDGFRA WT GIST, which results from the loss of function mutations in the genes encoding the SDH enzyme complex. The true frequency of SDH-deficient GISTs was reported to be approximately 7.4 to 7.7%. These tumours usually occur in the stomach (most commonly in the antrum) and have a spectrum of beha­viour from indolent to progressive. In most cases the molecular mechanism behind the SDH-deficient GISTs is connected to germline mutations. SDHA germline mutations occur in approximately 30% of the SDH-deficient GIST, those in SDHB , SDHC , and SDHD appear in 20–30% of patients. The SDH-mutated GISTs do not respond well to the commonly used targeted therapy, with no objective tumour response to imatinib. Taking into account the biological features of SDH-deficient GIST, new therapies of potential in­terest comprise PI3K/AKT/mTOR inhibitors, heat-shock protein inhibitors, HIF1-α targeting agents, epigenetic modifiers and demethylating agents. However, further research is necessary in these fields.

Exploration of a new method for Photoshop-assisted endoscopic ultrasound to distinguish gastrointestinal stromal tumor and leiomyoma

Background Gastrointestinal stromal tumors (GISTs) and leiomyomas (GILs) are difficult to be distinguished by endoscopic ultrasound (EUS). Photoshop software combined with EUS has limitations in distinguishing GIST and GIL by detecting gray values. Therefore, the research aims to explore the new method by Photoshop in distinguishing the features of GISTs from GILs. Methods Patients who underwent EUS and were confirmed as GIST and GIL pathologically were included. The images of EUS were analyzed by Photoshop software. The mean gray value of tumor (Tmean), muscularis propria (Mmean), submucosa (Smean), water (Wmean) and TSD that originated from the same image, were calculated one by one. Then the ratio of the mean gray value of tumor to muscularis propria (TMratio), submucosa (TSratio), and water (TWratio) were calculated, respectively. Results Four hundred seventy-two patients (239 GILs and 233 GISTs) were enrolled in this study retrospectively. All the tumors were located in the stomach. Tmean and TSD were significantly higher in GISTs than in the GILs group (63.10 ± 23.29 vs. 57.70 ± 22.67, p = .011; 26.24 ± 8.99 vs. 24.30 ± 8.26, p = .015). TMratio, TSratio, and TWratio were also significantly higher in GISTs group (0.97 ± 0.37 vs. 0.81 ± 0.28, p < .001; 0.42 ± 0.14 vs. 0.38 ± 0.12, p < .001; 2.65 ± 1.36 vs. 2.16 ± 1.02, p < .001). The AUC of Tmean was 0.952 (95% CI 0.897–1.000), which can better distinguish GIST from GIL; the sensitivity was 0.900, the specificity was 0.975, and the Youden Index was 0.875, and the cutoff was 79.64. The AUCs of TMratio, TSratio, and TWratio were 0.917 (95% CI 0.844–0.991), 0.897 (95% CI 0.812–0.981), and 0.929 (95% CI 0.8870–0.987), respectively. The aforementioned data was verified in the clinical cases of known results, including 40 GISTs and 40 GILs. The sensitivity of Tmean, TMratio, TSratio, and TWratio for diagnosis of GIL was 97.5%, 82.5%, 95%, and 97.5%, respectively. And they were 62.5%, 95%, 80%, and 92.5% for GIST. Conclusion The application of Photoshop combined with EUS to detect the gray value and standard deviation has a specific value in distinguishing GIST from GIL, but with some deviation. Applying the gray value ratio also has great discrimination significance and can avoid the differences in operation from different instrument and equipment personnel. Therefore, it is worthy of clinical promotion in the future.

Malignancy risk of gastrointestinal stromal tumors evaluated with noninvasive radiomics: A multi-center study.

PurposeThis study was to investigate the diagnostic efficacy of radiomics models based on the enhanced CT images in differentiating the malignant risk of gastrointestinal stromal tumors (GIST) in comparison with the clinical indicators model and traditional CT diagnostic criteria.Materials and methodsA total of 342 patients with GISTs confirmed histopathologically were enrolled from five medical centers. Data of patients wrom two centers comprised the training group (n=196), and data from the remaining three centers constituted the validation group (n=146). After CT image segmentation and feature extraction and selection, the arterial phase model and venous phase model were established. The maximum diameter of the tumor and internal necrosis were used to establish a clinical indicators model. The traditional CT diagnostic criteria were established for the classification of malignant potential of tumor. The performance of the four models was assessed using the receiver operating characteristics curve.ReusltsIn the training group, the area under the curves(AUCs) of the arterial phase model, venous phase model, clinical indicators model, and traditional CT diagnostic criteria were 0.930 [95% confidence interval (CI): 0.895-0.965), 0.933 (95%CI 0.898-0.967), 0.917 (95%CI 0.872-0.961) and 0.782 (95%CI 0.717-0.848), respectively. In the validation group, the AUCs of the models were 0.960 (95%CI 0.930-0.990), 0.961 (95% CI 0.930-0.992), 0.922 (95%CI 0.884-0.960) and 0.768 (95%CI 0.692-0.844), respectively. No significant difference was detected in the AUC between the arterial phase model, venous phase model, and clinical indicators model by the DeLong test, whereas a significant difference was observed between the traditional CT diagnostic criteria and the other three models.ConclusionThe radiomics model using the morphological features of GISTs play a significant role in tumor risk stratification and can provide a reference for clinical diagnosis and treatment plan.

Associations of CD34, Ki67, layer of invasion and clinical pathological characteristics, prognosis outcomes in gastrointestinal stromal tumors-a retrospective cohort study.

BackgroundGastrointestinal stromal tumors (GIST) is the most common interstitial tumor of the digestive tract. GIST, like other malignancies, can recur, metastasize, and even metastasize to the brain, leading to death. Therefore, the prevention and treatment of GIST is very important. The clinical features of GIST are uniquely different to those of other common malignancies. Therefore, it is of great significance to explore the relationship between the pathological features and prognosis of GIST to strengthen the prevention and treatment of GIST. The objectives of this study were to study the clinical features of Ki67, Cluster Differentiation 34 (CD34), and their correlations in the Jianghuai region of China in recent years, and to analyze their relationship with prognosis.MethodsA total of 423 cases of GIST in Northern Jiangsu People’s Hospital in Yangzhou from 2013 to 2020 were retrospectively analyzed. The data of CD34, Ki67 and layer of invasion was collected, and their associations with the clinical pathological characteristics, prognosis outcomes of GIST were studied. CD34 and Ki67 were tested by immunohistochemistry (IHC) And data was analyzed by chi-square test, t-test, Kaplan-Meier (KM) method survival curve, Log-rank test, and Cox regression.ResultsThe results showed that CD34 was associated with the clinical features of primary site, tumor size, risk, recurrence, and progression-free survival (PFS) (P<0.001, =0.01, <0.001, =0.039 and =0.018), but not with nuclear division or overall survival (OS) (P>0.05). Further, Ki67 was associated with nuclear division, tumor size, risk, recurrence, and PFS (P<0.001, <0.001, <0.001, <0.001 and <0.001), but there was no significant correlation with the primary site and CD34 (P>0.05), and Ki67 was associated with OS, but there was no statistical significance (P=0.0507). The layer of invasion was associated with the primary site, nuclear division, tumor size, risk, CD34, smooth muscle actin (SMA), recurrence, Ki67, and PFS (P<0.001, <0.001, <0.001, <0.001, <0.001, <0.001, <0.001, <0.001 and =0.0025), but not with OS (P=0.6680).ConclusionsCD34, Ki67, and layer of invasion may play important roles in the occurrence and development of GIST, affecting the prognosis of GIST.

Gastrointestinal Stromal Tümörlerin Klinikopatolojik Özellikleri ve Literatürün Gözden Geçirilmesi: Tek Merkez Deneyimi

Objective: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasias of the gastrointestinal system (GIS). The malignancy potential of GISTs may vary ranging from indolent tumors to progressive malignant tumors. This study aims to define clinicopathological and immunohistochemical features of GISTs diagnosed in our institute with a review of the literature.&#x0D; Method: A total of 28 GIST cases were included in the study. The Hematoxylin&amp;Eosin stained slides of surgical resection materials and cell blocks and immunohistochemistry performed slides were reviewed by a pathologist. The immunohistochemical expression with CD117, DOG-1, CD34, SMA, and S100 was scored between 0 and 3 points according to staining intensity. Descriptive statistics were used in the study. The demographic data, prognostic histopathological, and immunohistochemical findings are evaluated with the literature indications.&#x0D; Result: Eleven of the cases were male and seventeen were female. The age range was 18-88. The most common site of GISTs was the stomach, followed by the small intestine, colorectal region, and, esophagus. Twenty of the tumors were resected surgically, four were endoscopic biopsy material and four were fine-needle aspiration biopsies. The tumor size in measurable materials ranged from 0,2 to 22 cm. The mitotic count in 50 HPF ranges from 0 to 10. Seven of the GISTs were high grade and the remaining 21 were low grade. The majority of the cases were composed of spindle cells, 3 were epithelioid and 3 were the mixed type with spindle and epitheloid cells.&#x0D; Conclusion: A variety of criteria has been proposed to estimate the malignancy potential of GISTs and predict prognosis but definite prognostic criteria remain uncertain. Further studies with larger series of GISTs consisting of different types of biopsy materials may help define criteria to predict prognosis precisely.

Molecular heterogeneity and analysis of the long-term survival of patients with gastrointestinal stromal tumors

Introduction. Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract the character diagnostic feature of which is CD117 (KIT) expression. GISTs are clinically diverse and have different genetic alterations that may have predictive and prognostic significance.Aim – the study of clinical, morphological and genetic features of GISTs to assess the overall survival (OS) of patients with various profiles of genetic disorders for elucidation the factors contributing to prognosis.Materials and methods. A total 244 GIST patients who received combined treatment were enrolled in the study and their clinical characteristics and mutational status of KIT, PDGFRA, BRAF were analyzed. SDH-deficient GISTs were detected using IHC-analysis of SDHB expression.Results. Stromal tumors developed in stomach (50 %), small intestine (37.7 %), colon or rectum (8.6 %), esophagus (0.4 %) and extraorganically (EGIST, 5.7 %). Overall survival correlated with gastric site (p = 0.005), tumor size &lt;10 cm (p = 0,0001) and mitotic count HPF&lt; 10 / 50 (p = 0.007). KIT mutations were found in 168 (68.9 %) and PDGFRA – in 31 (12.1 %) of GISTs, 14 novel mutations were detected. Mutations in KIT exon 11 were found in 140 (57.4 %) tumors, 10-year OS, 51 %, median 124 months. Patients with deletions had lower OS than patients with substitutions or duplications in KIT exon 11 (p = 0,023). The lowest OS was in patients with primary mutations in KIT exons 13 or 17 (median 28 months) and duplications in KIT exon 9 (median 71 months). There was a low OS of young patients with homozygous KIT mutations, mutations that begin in intron and two simultaneous KIT mutations. GISTs with PDGFRA mutations were located in stomach and had no metastases, 10-year OS, 63 %, median 175 months. KIT / PDGFRA mutations were not observed in 45 (18.4 %) patients (wild-type GIST), 10-year OS, 59 %, median 250 months. Wild-type GISTs with BRAF, NF1 mutations and SDH deficiency were detected. The better OS was demonstrated by patients with BRAFV600E (10-year ОS, 84 %, median 97 months) and SDH deficiency (10-year and 15-year OS, 82 %).Conclusion. Genetic analysis is necessary to clarify GIST prognosis and predict the effectiveness of targeted therapy. The clinical, morphological and genetic diversity of GISTs was confirmed. Wild-type GISTs with BRAF mutations and SDHdeficiency were identified in the Russian population for the first time. The long-term 10- и 15-year OS of GIST patients were evaluated.

Gastrointestinal stromal tumors with Kit gene mutation in 4 guinea pigs (Cavia porcellus).

Gastrointestinal stromal tumors (GISTs) have been rarely reported in guinea pigs. We aimed to characterize the clinical and pathological features of GISTs in 4 guinea pigs and investigate the presence of mutations in exon 11 of the KIT proto-oncogene receptor tyrosine kinase (Kit) gene. Two subjects were male and 2 were female; 2 were 6 years old, 1 was 7 years old, and 1 was of an unknown age. Three cases had primary gastric tumors, whereas 1 had a primary small intestinal tumor. All cases had tumors that extended from the submucosa to the serosa with extraluminal growth. A gastric tumor had gastric, pancreatic, and cecal metastases. Histologically, the tumors were sharply demarcated and composed of spindle cells arranged in bundles, intermixed with small amounts of collagenous stroma. The tumor cells had mild atypia with few mitotic figures (0-5/50 high power fields, 7.95 mm2) and were immunolabeled for KIT and Discovered-on-GIST 1 (DOG1). All cases had mutations in exon 11 of the Kit gene. These findings indicate that GISTs in guinea pigs are similar to those in humans and dogs. GISTs in guinea pigs are potentially malignant submucosal tumors with KIT- and DOG1-immunolabeling, exon 11 KIT mutations, and the possibility of metastasis.