CD117, DOG1 and KI67 Expression in Gastrointestinal Stromal Tumours (original) (raw)
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Egyptian Journal of Pathology, 2014
Introduction Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Most GISTs show a positive immunoreactivity for C-KIT. However, a small group (about 5%) is KIT negative, leaving the diagnosis in question. KITnegative GISTs harbor KIT or platelet-derived growth factor receptor-a mutations, and thus may be sensitive to imatinib therapy. Molecular screening may help in such cases, but it adds to the time and the cost of diagnosis. The 'discovered on GIST-1' (DOG1) antibody has emerged in recent years as a promising biomarker for GISTs. We evaluated the immunohistochemical expression of DOG1 in GIST cases and compared it with C-KIT regarding the sensitivity. Results C-KIT was positively immunostained in 94% and DOG1 was positive in 98% of the cases. All three KITnegative cases were positive for DOG1, and C-KIT was positive in the DOG1-negative case. DOG1 showed a higher sensitivity than C-KIT in the diagnosis of suspected GIST. Conclusion A combination of DOG1 and C-KIT immunostaining is sufficient to confirm the diagnosis in histologically suspected GIST cases in order not to miss patients who could benefit from therapy. Egypt J Pathol
https://www.ijrrjournal.com/IJRR\_Vol.9\_Issue.8\_Aug2022/IJRR-Abstract56.html, 2022
Introduction: Gastrointestinal stromal tumors are the most common mesenchymal tumors in the gastrointestinal tract. The diagnosis of GISTs becomes much more accurate by using IHC (CD117/DOG1) and molecular analysis (KIT/PDGFRA), both of which constitute the gold standard of diagnosis in GISTs. Aim: The study was conducted in a tertiary care hospital in western India between January, 2019 to June 2020 to evaluate clinic pathological correlation & agreement between CD117 and DOG1 antibodies that are employed in diagnosis of GIST. Material & Methods: The cases were selected on the basis of inclusion & exclusion criteria defined and thereafter a panel of CD117, DOG1 and other antibodies was applied to diagnose GIST from other mesenchymal tumors of gastrointestinal tract. Results: The average age of the patient was 53.5 years with male preponderance was noted. (M:F=1.66). The clinical complaints included: GI Bleeding (50%), Abdominal pain (30%), lump abdomen (20%).Most common site for GIST was gastric (50%) followed small intestine (40%), mesentry-omentum (7.50%) and colon (2.50%). Spindle cell morphology (75.00%) was the most common histomorphological subtype. DOG1 antibody diagnosed 97.50 % cases of GIST and CD117 diagnosed 92.50% cases of GIST. DOG1 expressed high staining ratio score in 95% cases while CD117 had high staining ratio score in 87.50% cases. Mostly stronger intensity of immunostaining was observed with DOG1 while CD117 expressed variable intensity of immunostaining. Also, CD117 expressed variable immunostaining amongst different histomorphological variants and risk groups. While immunostaining with DOG1 was not significantly variable. The results demonstrated that DOG-1 was found to be a superior marker with higher sensitivity and specificity as compared to CD117, specificity (100% versus 96.43%) and sensitivity (97.5% versus 92.5%). Conclusion: The immunohistochemistry panel should be applied in stepwise manner over “morphologically suspicious” cases Mesenchymal Tumours of GIT to diagnose and rule out GIST with first panel being CD117 and DOG1. DOG-1 was found to be a superior marker with higher sensitivity and specificity as compared to CD117. Cases negative for all the antibodies should definitely be referred for molecular analysis to detect other mutations of GIST (kit/PDGFRA negative wild type GIST).
Annals of African Medicine, 2023
Original Article Aims: Gastrointestinal stromal tumors (GISTs) are neoplastic lesions that primarily affect the digestive tract and develop from interstitial cells of Cajal. These lesions require histopathological and immunohistochemical characterization due to their malignant potential and personalized treatment. In this investigation, the sex, age, lesional sites of origin, histopathological types, the prevalence of human epidermal growth factor receptors (HER-2) expression, prognostic indices (based on tumor size and mitotic figures), expression of CD117 and DOG1, and characteristics of patients with GIST were all characterized. Materials and Methods: This was a retrospective cross-sectional analysis of GIST cases seen at four tertiary health-care centers in Nigeria over a 10-year period (2008-2017) and investigated utilizing histopathological and immunohistochemical (CD117, DOG1, and HER-2) methods. Results: In this investigation, there were twenty GIST cases. Notably, the majority (40%) of the cases had tumors with sizes between 7.0 and 8.0 cm; the stomach was the most frequent site (70%) and the spindle cell type of GIST was the most prevalent (80%) histopathological type. In addition, the stomach was significantly associated with GIST as an origin site (with a P = 0.001), and 100% and 50% of these tumors were immunoreactive with CD117 and DOG1, respectively. Conclusions: In our study, GISTs most frequently develop in the stomach, and CD117 and DOG1 are essential for correctly diagnosing these tumors. However, HER-2 immunoreactivity is a predictive marker of survival for personalized care.
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DOG1 Antibody in the Differential Diagnosis of Gastrointestinal Stromal Tumors
American Journal of Surgical Pathology, 2009
Gastrointestinal Stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Their cellular origins are found in cells of Cajal which are responsible of the induction and regulation of peristalsis and smooth muscle (1). GISTs are rare in the soft tissue sarcomas but have particular interest because since the 2000s enormous progress was performed about: Nosological identification by molecular biology Endoscopic and radiological studies. Knowledge of prognostic factors. Development of targeted therapies All this has led to a significant improvement of prognosis with a median survival that goes from 12 to 50 months in the metastatic setting. Evolution of concepts and carcinogenesis: Recent years have experienced a revolution in the understanding of oncogenesis of these tumors. GISTs were first classified as conjunctival tumors based on the histogenesis. The development of immunohistochemistry (IHC) allowed to orientate the diagnosis into muscular origin based of Actin positivity, neurogenic origin by the positivity of the PS100 and mesenchymal origin by CD34 positivity. However no specific markers of this cell line was available. (2) The 2000s were marked by a revolution in the understanding of GIST by identifying the c-KIT and its expression by IHC CD117. The c-KIT is a trans-membrane tyrosine kinase receptor that once linked to its specific ligand SCF (stem cell factor) will trigger a signaling cascade leading to activation of apoptosis, differentiation, and cell adhesion. GISTs are characterized by an activating mutation of the ckit which will cause uncontrolled cell proliferation and resistance to apoptosis. (3) The second step in the understanding of oncogenesis of GIST was reached due to advances in molecular biology with the identification of activating mutations that will often concern the KIT or PDGFRa genes. The search for these mutations will allow the positive diagnosis and having prognosis and predictive factor of response to treatment. (4) Epidemiology The annual incidence is of around 2000-5000 cases / year in the United States and 400-600 cases / year in France. The average age is 40 to 60 years with some pediatric cases remaining exceptionals. The sex ratio is 1.
Balkan Medical Journal, 2015
Background: Gastrointestinal stromal tumors (GIST) have KIT or platelet-derived growth factor receptor α (PDGFRα) mutations affecting receptor tyrosine kinase activity and do not benefit from classic treatment regimens. Aims: The aim of this study was to review the algorithm that may be followed for the diagnosis and differential diagnosis in GISTs by investigating the histomorphological parameters and expression characteristics of classical immunohistochemical antibodies used in routine tests in addition to DOG1 expression. Study Design: Diagnostic accuracy study. Methods: We reevaluated the histological and immunohistochemical parameters of 37 GISTs. The standard immunohistochemical diagnosis and differential diagnosis panel antibodies (CD117, PDGFRα, CD34, vimentin, desmin, SMA, S-100, and Ki67) were studied on the tumor sections. We also used the popular marker DOG1 antibody with accepted sensitivity for GISTs in recent years and the PDGFRα immune marker for which the benefit in routine practice is discussed. Results: Classification according to progressive disease risk groups of the 37 cases revealed that 54% were in the high risk, 19% in the moderate risk, 16% in the low risk, 8% in the very low risk and 8% in the no risk group. Cytological atypia, necrosis, mucosal invasion and the Ki67 index were found to be related to the progressive disease risk groups of the tumors (p<0.05). Positive immunoreaction was observed with CD117 and PDGFRα in all GISTs in the study (100%). Positivity with the DOG1 antibody was found in 33 (89%) cases. CD34 was positive in 62% (23) of the cases. Conclusion: The CD117 antibody still plays a key role in GIST diagnosis. However, the use of DOG1 and PDGFRα antibodies combined with CD117 as sensitive markers can be beneficial.
Gastrointestinal stromal tumours(GISTs) negative for KIT(CD117 antigen) immunoreactivity
The Journal of Pathology, 2004
Gastrointestinal stromal tumours (GISTs) are currently defined as mesenchymal tumours of the gastrointestinal tract that express KIT receptor tyrosine kinase. However, a small subgroup of tumours that fulfil the clinical and morphological criteria for GISTs lack KIT expression. So far, the biological features of these tumours have rarely been addressed. The present study describes seven gastrointestinal stromal neoplasms that presented clinicopathological features typical of GISTs but showed absence of CD117 expression as detected by immunohistochemistry. The tumours originated from the stomach (n = 5), duodenum (n = 1), and colon (n = 1), showing histologically either predominantly epithelioid (n = 3), mixed spindled and epithelioid (n = 2), or anaplastic/spindle cell (n = 2) type features. CD34 and α-smooth muscle actin (α-SMA) positivity was present in four and three tumours, respectively. Chromosomal analysis was performed in two cases, both showing losses of chromosomes 14, 22, and 1p, which is the characteristic feature of GISTs. Dual-colour interphase fluorescence in situ hybridization (FISH) analysis, utilizing chromosome 1p-, 14-, and 22-specific probes, revealed a similar cytogenetic profile in the remaining five tumour specimens. Mutational analysis of exons 9, 11, 13, and 17 of KIT, and exons 12 and 18 of PDGFRA was performed in all cases by denaturing highpressure liquid chromatography (DHPLC) pre-screening, followed by direct sequencing. None of the tumours showed KIT mutant isoforms. Three tumours harboured PDGFRA exon 18 activating mutations; two were Asp → Val 842 missense substitutions and one was a DIM842-844 amino acid deletion. KIT and PKCθ (protein activated in interstitial cells of Cajal and GISTs) expression was determined by western immunoblotting of the total cell lysates from three tumour biopsies. None of these three tumours expressed KIT, while all specimens showed expression of PKCθ protein. These findings indicate that there is a subgroup of KIT-negative GISTs that exhibit the same morphological, cytogenetic, and molecular features as KIT-positive tumours. While intragenic PDGFRA activating mutations are present in some of these tumours, the oncogenic events underlying the pathogenesis of the others remain unknown.
Nigerian journal of clinical practice, 2010
Mesenchymal tumours of the gastrointestinal tract (GIT) are uncommon. Recent progress in the understanding of the biology and origin of these tumours has led to their reclassification. A new subclass designated Gastrointestinal Stromal Tumours (GIST) is diagnosed based on the presence of a mutational over expression of c-kit protein that is thought to be critical in the pathogenesis of these tumours. This new class oftumours may form the majority of gastrointestinal mesenchymal tumours. Even though the diagnosis of GIST is mainly based on positive staining with CD117, a minority of tumours with histological characteristics of GIST are CD117 negative and are classified as CD117 negative GIST. In this first review of mesenchymal GIT tumours from Nigeria, we present 11 cases ofmesenchymal tumours of the gastrointestinal tract seen within a six-year period at our centre. Immunohistochemistry was performed on 7 of them in which histological appearances suggested GIST. Only two cases had ...
IP innovative publication pvt. ltd, 2019
Introduction: Mesenchymal tumours of gastrointestinal tract are a heterogenous group of nonepithelial tumours of variable mesenchymal cell histogenesis. Gastrointestinal stromal tumour (GIST) is the most common primary mesenchymal tumour of the gastrointestinal tract and spans a clinical spectrum from benign to malignant. This study evaluated the clinicopathological morphological and immunohistochemical features of GIST of the intestinal tract. Materials and Methods: All evaluable cases of mesenchymal tumors of the gastrointestinal tract were studied from January 2007 to December 2012. Tissue microarray was constructed and Immunohistochemical expression of CD 117, CD 34, DOG1, SMA, S100, Ki 67 were studied. Results: Gastrointestinal stromal tumours were the most common mesenchymal tumours of the gastrointestinal tract accounting to 77.96%. The median age of presentation was 51 years with near equal sex preliction with early clinical presentation. The gastric tumours were of significantly bigger size with increased expression of CD 34. Majority of tumors were of bigger size (>10 cm, 47%) thereby increased number of tumours in high risk category (76%). Spindle cell pattern was the most common morphology (69.5%). Epitheliod histology was significantly associated with pleomorphism and atypia (p value – 0.029). Inclusion of anatomic site into the risk category will help in better stratificaion. High risk tumours showed significant areas of necrosis when compared with low risk tumours (p value- 0.0156). Tumours of older age group (>40 years) showed significant mitotic activity (p value 0.04). DOG1 is a very sensitive (97.8%) marker for GIST. A wide immunopanel with emphasis on DOG 1 positivity for precise diagnosis of GIST and classification of mes enchymal tumors of the GI tract.
Cancers
Gastrointestinal stromal tumors (GISTs) originating from the interstitial cells of Cajal are mesenchymal tumors of the gastrointestinal tract and have been found to harbor c-KIT mutations and KIT (CD117) expression since 1998. Later, PDGFRA mutations, SDH alterations, and other drive mutations were identified in GISTs. In addition, more and more protein markers such as DOG1, PKCθ were found to be expressed in GISTs which might help clinicians diagnose CD117-negative GISTs. Therefore, we plan to comprehensively review the molecular markers and genetics of GISTs and provide clinicians useful information in diagnostic and therapeutic strategies of GISTs. Twenty years after the discovery of KIT in GISTs, the diagnosis of GISTs became much more accurate by using immunohistochemical (IHC) panel (CD117/DOG1) and molecular analysis (KIT/PDGFRA), both of which constitute the gold standard of diagnosis in GISTs. The accurately molecular diagnosis of GISTs guides clinicians to precision medici...