Deep Convolutional Neural Networks Detect Tumor Genotype from Pathological Tissue Images in Gastrointestinal Stromal Tumors

Gastrointestinal stromal tumors (GIST) are common mesenchymal tumors, and their effective treatment depends upon the mutational subtype of the KIT/PDGFRA genes. We established deep convolutional neural network (DCNN) models to rapidly predict drug-sensitive mutation subtypes from images of pathological tissue. A total of 5153 pathological images of 365 different GISTs from three different laboratories were collected and divided into training and validation sets. A transfer learning mechanism based on DCNN was used with four different network architectures, to identify cases with drug-sensitive mutations. The accuracy ranged from 87% to 75%. Cross-institutional inconsistency, however, was observed. Using gray-scale images resulted in a 7% drop in accuracy (accuracy 80%, sensitivity 87%, specificity 73%). Using images containing only nuclei (accuracy 81%, sensitivity 87%, specificity 73%) or cytoplasm (accuracy 79%, sensitivity 88%, specificity 67%) produced 6% and 8% drops in accuracy rate, respectively, suggesting buffering effects across subcellular components in DCNN interpretation. The proposed DCNN model successfully inferred cases with drug-sensitive mutations with high accuracy. The contribution of image color and subcellular components was also revealed. These results will help to generate a cheaper and quicker screening method for tumor gene testing.

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Multislice imaging of gastrointestinal stromal tumors

10.32512/jmr.1.1.2018/3.14 ◽

2018 ◽

pp. 3-14

Keyword(s):

Computed Tomography ◽

Key Words ◽

Gold Standard ◽

Gastrointestinal Stromal Tumors ◽

Mesenchymal Tumors ◽

Stromal Tumors ◽

Preferential Localization ◽

Multislice Imaging ◽

Computed Tomography Diagnosis

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the digestive tract (1%). These tumors express the CD 117 in 95% of cases. The stomach is the preferential localization (70%). Diagnosis is difficult and sometimes late. Progress of imaging has greatly improved the management and the prognosis. Computed tomography (CT) is the gold standard for diagnosis, staging, and treatment follow-up. The increasing recognition of GIST’s histopathology and the prolonged survival revealed some suggestive imaging aspects. Key words: gastro-intestinal stromal tumors; computed tomography; diagnosis

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Gastrointestinal Stromal Tumors (GISTs): Novel Therapeutic Strategies with Immunotherapy and Small Molecules

International Journal of Molecular Sciences ◽

10.3390/ijms22020493 ◽

2021 ◽

Vol 22 (2) ◽

pp. 493

Author(s):

Christos Vallilas ◽

Panagiotis Sarantis ◽

Anastasios Kyriazoglou ◽

Evangelos Koustas ◽

Stamatios Theocharis ◽

...

Keyword(s):

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Gastrointestinal Stromal Tumors ◽

Kinase Inhibitors ◽

Checkpoint Inhibitors ◽

Survival Rates ◽

Cancer Therapeutics ◽

Gastrointestinal Neoplasms ◽

Mesenchymal Tumors ◽

Stromal Tumors

Gastrointestinal stromal tumors (GISTs) are the most common types of malignant mesenchymal tumors in the gastrointestinal tract, with an estimated incidence of 1.5/100.000 per year and 1–2% of gastrointestinal neoplasms. About 75–80% of patients have mutations in the KIT gene in exons 9, 11, 13, 14, 17, and 5–10% of patients have mutations in the platelet-derived growth factor receptor a (PDGFRA) gene in exons 12, 14, 18. Moreover, 10–15% of patients have no mutations and are classified as wild type GIST. The treatment for metastatic or unresectable GISTs includes imatinib, sunitinib, and regorafenib. So far, GIST therapies have raised great expectations and offered patients a better quality of life, but increased pharmacological resistance to tyrosine kinase inhibitors is often observed. New treatment options have emerged, with ripretinib, avapritinib, and cabozantinib getting approvals for these tumors. Nowadays, immune checkpoint inhibitors form a new landscape in cancer therapeutics and have already shown remarkable responses in various tumors. Studies in melanoma, non-small-cell lung cancer, and renal cell carcinoma are very encouraging as these inhibitors have increased survival rates. The purpose of this review is to present alternative approaches for the treatment of the GIST patients, such as combinations of immunotherapy and novel inhibitors with traditional therapies (tyrosine kinase inhibitors).

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Skeletal Muscle Metastasis of a GIST: A Case Report and Review of the Literature

Case Reports in Surgery ◽

10.1155/2016/7867545 ◽

2016 ◽

Vol 2016 ◽

pp. 1-5

Author(s):

Olga D. Savvidou ◽

George D. Chloros ◽

Georgios D. Agrogiannis ◽

Penelope Korkolopoulou ◽

Georgios N. Panagopoulos ◽

...

Keyword(s):

Skeletal Muscle ◽

Case Report ◽

Soft Tissue ◽

Gastrointestinal Stromal Tumors ◽

Review Of The Literature ◽

Soft Tissue Metastasis ◽

Mesenchymal Tumors ◽

Stromal Tumors ◽

Skeletal Muscle Metastasis ◽

Muscle Metastasis

Gastrointestinal stromal tumors (GISTs) are the most common malignant mesenchymal tumors of the gastrointestinal tract. The most common sites of metastasis are the liver and the peritoneum, whereas metastasis to soft tissue is rare. The authors present the case of a 78-year-old male with a soft tissue metastasis of a GIST and the current literature is reviewed.

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Imatinib in the Management of Multiple Gastrointestinal Stromal Tumors Associated With a Germline KIT K642E Mutation

Archives of Pathology & Laboratory Medicine ◽

10.5858/2007-131-1393-iitmom ◽

2007 ◽

Vol 131 (9) ◽

pp. 1393-1396

Author(s):

Janet Graham ◽

Maria Debiec-Rychter ◽

Christopher L. Corless ◽

Robin Reid ◽

Rosemarie Davidson ◽

...

Keyword(s):

Gastrointestinal Stromal Tumors ◽

Interstitial Cells Of Cajal ◽

Germline Mutations ◽

Mesenchymal Tumors ◽

Stromal Tumors ◽

Pdgfra Gene ◽

Oncogenic Mutations ◽

Esophageal Tumors ◽

Exon 11 ◽

Cells Of Cajal

Abstract Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gut and are distinguished by expression of CD117 (c-Kit). Oncogenic mutations in the KIT or PDGFRA gene are detected in approximately 85% of sporadic GISTs. In recent years, examples of familial GIST have been reported in which germline mutations of KIT or PDGFRA result in multiple GISTs, skin disorders, and other abnormalities. The most common germline mutations are in KIT exon 11, mutations in exons 8 and 17 have also been described, and there are 2 families with germline PDGFRA mutations. We present a case in which a germline KIT exon 13 mutation (K642E) was discovered in a patient with multiple GISTs of rectum, small intestine, and esophagus, as well as diffuse hyperplasia of the interstitial cells of Cajal. To our knowledge, this is only the second germline example of this particular mutation. The patient's esophageal tumors were stabilized with imatinib.

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Gastric schwannoma: a benign tumor often misdiagnosed as gastrointestinal stromal tumor

Clinics and Practice ◽

10.4081/cp.2015.775 ◽

2015 ◽

Vol 5 (3) ◽

Cited By ~ 7

Author(s):

Apurva S. Shah ◽

Pravin M. Rathi ◽

Vaibhav S. Somani ◽

Astha M. Mulani

Keyword(s):

Differential Diagnosis ◽

Gastrointestinal Stromal Tumor ◽

Gastrointestinal Stromal Tumors ◽

Rare Case ◽

Benign Tumor ◽

Stromal Tumor ◽

Mesenchymal Tumors ◽

Stromal Tumors ◽

Gastric Schwannoma ◽

Gastric Mass

Gastric schwannomas are rare mesenchymal tumors that arise from the nerve plexus of gut wall. They present with nonspecific symptoms and are often detected incidentally. Preoperative investigation is not pathognomic and many are therefore misdiagnosed as gastrointestinal stromal tumors. We report a rare case of a 37-year old woman who underwent laparotomy for complex bilateral ovarian cyst with resection of gastric-gastrointestinal stromal tumor preoperatively, but confirmed to have a gastric schwannomas postoperatively. This case underscores the differential diagnosis of submucosal, exophytic gastric mass as schwannoma.

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The importance of molecular biology in development, prognosis, treatment and resistance to targeted therapy in gastrointestinal stromal tumors

Oncology Reviews ◽

10.4081/oncol.2008.112 ◽

2011 ◽

pp. 69-79

Author(s):

Alessandro Comandone ◽

Elisa Berno ◽

Simona Chiadò Cutin ◽

Antonella Boglione

Keyword(s):

Tyrosine Kinase ◽

Gastrointestinal Stromal Tumors ◽

Kinase Inhibitors ◽

Growth Factor Receptor ◽

Neoplastic Transformation ◽

Response To Therapy ◽

Mesenchymal Tumors ◽

Kit Mutation ◽

Stromal Tumors ◽

Receive Treatment

Gastrointestinal stromal tumors (GISTs) are the commonest mesenchymal tumors of the gastroenteric tract, and are generally believed to originate from the neoplastic transformation of the interstitial cells of Cajal, the pacemaker structures of the stomach and intestine. Exon and genetic mutations (point/deletions) are fundamental for the development of GISTs: the constitutional characteristic of this neoplasm is the presence of the cell surface Kit receptor. Kit is the product of the proto-oncogene cKit, situated in chromosome 4. Ninety-eight percent of GISTs express mutated isoforms of Kit or of PDGFRA (Platelet growth factor receptor a). Kit mutation is the basic condition for autophosphorylation of tyrosine kinase residues in proteins. Autophosphorylation initiates pathogenetic processes in Cajal cells, toward a neoplastic transformation. Imatinib mesilate and, more recently, sunitinib are tyrosine kinase inhibitors, specific antagonists for Kit and PDGFRA, with good activity against GISTs. Most molecular and clinical data currently available concern imatinib. Exon mutations are strategic as prognostic and as predictive factors. In recent years, much evidence suggests that survival, response to therapy and resistance to imatinib are related to different mutations. In the near future, GIST patients will receive treatment differentiated by expressed Kit and PDGFRA mutations, thus truly individualized therapy.

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Gastrointestinal Stromal Tumors (GISTs): From Science to Targeted Therapy

The International Journal of Biological Markers ◽

10.1177/172460080802300206 ◽

2008 ◽

Vol 23 (2) ◽

pp. 96-110 ◽

Cited By ~ 3

Author(s):

R. Sarmiento ◽

P. Bonginelli ◽

F. Cacciamani ◽

F. Salerno ◽

G. Gasparini

Keyword(s):

Targeted Therapy ◽

Tyrosine Kinase ◽

Gastrointestinal Stromal Tumors ◽

Kinase Inhibitor ◽

Mesenchymal Tumors ◽

Treatment Scenario ◽

Stromal Tumors ◽

Imatinib Resistant ◽

Review Reports ◽

Molecular Patterns

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. GISTs represent a distinct category of tumors characterized by oncogenic mutations of the KIT receptor tyrosine kinase in a majority of patients. KIT is useful not only for the diagnosis but also for targeted therapy of this disease. Imatinib, a tyrosine kinase inhibitor, is widely used in advanced and metastatic GISTs. This agent revolutionized the treatment strategy of advanced disease and is being tested in the neoadjuvant and adjuvant settings with encouraging results. New therapeutic agents like sunitinib have now been approved, enriching the treatment scenario for imatinib-resistant GISTs. The present review reports on the peculiar characteristics of this disease through its biology and molecular patterns, focusing on the predictive value of KIT mutations and their correlation with clinical outcome as well as on the activity of and resistance to approved targeted drugs.

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Large Omental Metastases of a Gastrointestinal Stromal Tumor

Medicina ◽

10.3390/medicina47110086 ◽

2011 ◽

Vol 47 (11) ◽

pp. 86

Author(s):

Povilas Ignatavičius ◽

Tomas Petraitis ◽

Žilvinas Saladžinskas ◽

Lilija Butkevičienė ◽

Kristina Žvinienė

Keyword(s):

Case Report ◽

Gastrointestinal Tract ◽

Gastrointestinal Stromal Tumor ◽

Gastrointestinal Stromal Tumors ◽

Interstitial Cells Of Cajal ◽

Metastatic Tumor ◽

Stromal Tumor ◽

Mesenchymal Tumors ◽

Stromal Tumors ◽

Cells Of Cajal

Gastrointestinal stromal tumors are rare tumors, originating from the interstitial cells of Cajal. They are the most common mesenchymal tumors of the gastrointestinal tract. Metastatic tumor is treated with imatinib mesylate. A case of large metastases of a gastrointestinal stromal tumor to the omentum, diagnosis and treatment principles are presented in this case report.

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Gallbladder GIST: A review of literature

Polish Journal of Surgery ◽

10.5604/01.3001.0013.5550 ◽

2019 ◽

Vol 92 (1) ◽

pp. 1-5

Author(s):

Ashish Gupta

Keyword(s):

Gastrointestinal Stromal Tumors ◽

Interstitial Cells Of Cajal ◽

Case Reports ◽

Gallbladder Wall ◽

Postoperative Adjuvant Therapy ◽

Review Of Literature ◽

Mesenchymal Tumors ◽

Stromal Tumors ◽

Extensive Search ◽

Cells Of Cajal

Mesenchymal tumors of the gallbladder are rarely encountered in clinical practice. The Gastrointestinal Stromal tumors(GIST) of the gallbladder are rarely encountered. These tumors most commonly arise from the interstitial cells of cajal(ICC), the pacemakers of the intestinal system. There can be benign as well as malignant form of GIST .The literature on GIST arising from the gallbladder wall is limited to few case reports only.on extensive search of the indexed literature only 9 cases of gallbladder GIST were retrieved. Based on the available literature these tumors are commonly found in females. They usually present with hypochondrial pain with or without other features of cholangitis. These tumors are usually malignant and warrant a radical surgical excision.The data on postoperative adjuvant therapy and survival is limited. The authors are presenting a review of the available literature on this rare pathology.

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