DOG1 Antibody in the Differential Diagnosis of Gastrointestinal Stromal Tumors

Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, 6825 16th Street, NW, Building 54, Room G090,Washington, DC 20306-6000, USA.
The American journal of surgical pathology (Impact Factor: 5.15). 08/2009; 33(9):1401-8. DOI: 10.1097/PAS.0b013e3181a90e1a
Source: PubMed


Gastrointestinal stromal tumors (GISTs), KIT or platelet derived growth factor receptor alpha (PDGFRA) signaling driven mesenchymal tumors of the gastrointestinal (GI)-tract and abdomen, require a precise diagnosis so that the patients may benefit from the newly introduced tyrosine kinase inhibitor drugs. The limitations of the current main tools, KIT immunohistochemistry and KIT/PDGFRA mutation analysis, include lack of KIT expression and mutations in some GISTs. In this study we examined 1168 GISTs of different sites and histologic subtypes, and 672 other tumors and normal tissues for discovered on GIST-1 (DOG1) clone K9, a newly introduced immunohistochemical marker, a chloride channel protein. All GISTs and selected non-GISTs were independently evaluated for KIT. In the GI tract, Cajal cells and gastric surface epithelia were DOG1-positive. The overall sensitivity of DOG1 and KIT in GISTs was nearly identical: 94.4% and 94.7%, and results in GISTs were generally concordant. Gastric spindle cell GISTs was nearly uniformly positive for both markers, whereas DOG1 performed slightly better in gastric epithelioid GISTs that included PDGFRA mutant GISTs. In the intestinal GISTs, KIT was slightly more sensitive than DOG1. Negativity for both DOG1 and KIT was observed in 2.6% of GISTs of GI tract. KIT or PDGFRA mutations were detected in 11/24 DOG1-negative GISTs supporting the diagnosis of GIST. DOG1 expression was also generally present in extragastrointestinal and metastatic GISTs. DOG1 was highly specific for GIST, but exceptional DOG1-positive other mesenchymal tumors included uterine type retroperitoneal leiomyomas, peritoneal leiomyomatosis, and synovial sarcomas (positive in 5/42, 4/17, and 6/37 cases). Leiomyomas colonized by DOG1-positive Cajal cells should not be confused with GISTs. DOG1 positivity was relatively common in esophageal squamous cell and gastric carcinomas, whereas it was rare in colorectal carcinomas. DOG1 should be added into the diagnostic panel evaluating GI and other abdominal tumors, but limitations in its sensitivity and specificity should be recognized.

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    • "Other commonly expressed markers include CD34 antigen (70%), smooth muscle actin (SMA; 30 to 40%), desmin (<5%), and S100 protein (~5%) [24]. A recently described antibody against Discovered on GIST-1 (DOG1) has been reported to be as sensitive as KIT in diagnosing GIST, but DOG1 is expressed only in about 30% of KIT-negative GISTs, limiting its use in this setting [25]. "
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    ABSTRACT: For many years, the understanding of gastrointestinal stromal tumors (GISTs), which are the most common mesenchymal tumors of the gastrointestinal tract, has been very limited. However, it is now possible to provide a more precise definition through the use of pathology classification and molecular techniques. Coupled with the advancement of clinical practice, especially the development of targeted therapy, there is now a much better insight into its treatment. At present, organizations such as the National Comprehensive Cancer Network in the USA and the European Society for Medical Oncology in Europe have established a consensus and drawn up guidelines for the diagnosis, treatment, and follow-up of GISTs. With experts coming from various districts in Taiwan and combining the most recent clinical data and experiences, the Taiwan Surgical Society of Gastroenterology drafted the first national GIST treatment guidelines after a consensus meeting in 2007. Following subsequent advances in GIST diagnosis and treatment, further revisions and modifications have been made to the original guidelines. We present here the updated consensus and recommendations of the Taiwan Surgical Society of Gastroenterology for the diagnosis and treatment of GIST. We hope these guidelines can help enhance the quality of diagnosis, treatment, and care of patients with GIST in Taiwan.
    World Journal of Surgical Oncology 11/2012; 10(1):246. DOI:10.1186/1477-7819-10-246 · 1.41 Impact Factor
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    • "Identification of CD117-negative GIST remains a diagnostic challenge, and these are most likely to be driven by alternative kinases like PDGFRA [33]. The antigen known as DOG-1 (“discovered on GIST-1”) can also help to identify certain KIT-negative GIST lesions as DOG-1 expression is quite specific for GIST [34,35]. "
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    ABSTRACT: Stromal or mesenchymal neoplasms affecting the gastrointestinal (GI) tract have undergone a remarkable evolution in how they are perceived, classified, approached, diagnosed and managed over the last 30 years. Gastrointestinal stromal tumors (GIST) account for approximately 1% to 3% of all malignant GI tumors. The clinical features can vary depending on the anatomic location, size and aggressiveness of the tumor. Metastatic GIST represents a successful example of molecular targeted therapy. In this comprehensive review, we discuss the epidemiology, clinical features and diagnostic modalities for GIST. We also describe treatment options for early stage, locally advanced and metastatic GIST. Indications for neoadjuvant and adjuvant therapy along with duration of therapy are also explained. A brief discussion of latest biomarkers and updates from recent meetings is also provided.
    06/2012; 1(1):14. DOI:10.1186/2162-3619-1-14
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    • " frequently. In recent years, with the development of effective targeted therapies for GISTs, the prognosis of GISTs patients is significantly improved and accurate diagnosis of GISTs become important, especially for the KIT absent GISTs . DOG1 ( discovered on GIST - 1 ) is a newly identified marker of GISTs , which is almost as sensitive as KIT ( Miettinen et al . , 2009 ) . DOG1 is a kind of chloride ion channel proteins regulated by calcium , however , the function of DOG1 remains unclear ."
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    ABSTRACT: To discuss the significance of DOG1, CD117 and PDGFRA in the diagnosis of gastrointestinal stromal tumors (GISTs), and analyze their correlations with clinicopathological features and risk ranking. DOG1, CD117 and PDGFRA were detected with IHC Envision ldpe-g-nvp in 63 GISTs and 43 cases of non-GISTs, and analyzed for relations with clinicopathological factors (gender, age, location, tumor size, mitotic phase, histology) and risk degree. The positive expression rate of DOG1, CD117 and PDGFRA in GISTs was 84.1% (53/63), 90.5% (57/63), 53.2% (33/63), respectively. Among the 6 CD117 negative cases, all were DOG1 positive and 5 were PDGFRA positive. Rates in patients with non-GISTs was 11.6%, 16.3%, 6.98%, respectively. Expression of DOG1 and PDGFRA demonstrated no significant variation with gender, age, position, tumor size, mitotic phase, histology, and risk rank. However, CD117 was related with position and histology (P=0.008 and P=0.045), those in the mesentery having a higher positive rate than those derived from stomach, small intestine, colon and rectum (50.0% vs 94.7%, P=0.008). Furthermore CD117 was also highly expressed in spindle and epithele types. DOG1 had a good sensitivity and specificity as a kind of newly discovered marker, especially for KIT negative GISTs. However, DOG1, CD117 and PDGFRA cannot be used for assessing the rish of patients.
    Asian Pacific journal of cancer prevention: APJCP 04/2012; 13(4):1389-93. DOI:10.7314/APJCP.2012.13.4.1389 · 2.51 Impact Factor
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