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Espinosa I, Lee CH, Kim MK, et al. A novel monoclonal antibody against DOG1 is a sensitive and specific marker for gastrointestinal stromal tumors

Department of Pathology, Stanford University Medical Center, Stanford, CA 94305, USA.
American Journal of Surgical Pathology (Impact Factor: 4.59). 03/2008; 32(2):210-8. DOI: 10.1097/PAS.0b013e3181238cec
Source: PubMed

ABSTRACT Gastrointestinal stromal tumors (GIST) occur primarily in the wall of the intestine and are characterized by activating mutations in the receptor tyrosine kinases genes KIT or PDGFRA. The diagnosis of GIST relies heavily on the demonstration of KIT/CD117 protein expression by immunohistochemistry. However, KIT expression is absent in approximately 4% to 15% of GIST and this can complicate the diagnosis of GIST in patients who may benefit from treatment with receptor tyrosine kinase inhibitors. We previously identified DOG1/TMEM16A as a novel marker for GIST using a conventional rabbit antipeptide antiserum and an in situ hybridization probe. Here, we describe 2 new monoclonal antibodies against DOG1 (DOG1.1 and DOG1.3) and compare their staining profiles with KIT and CD34 antibodies on 447 cases of GIST. These included 306 cases with known mutational status for KIT and PDGFRA from a molecular consultation service. In addition, 935 other mesenchymal tumors and 432 nonsarcomatous tumors were studied. Both DOG1 antibodies showed high sensitivity and specificity for GIST, with DOG1.1 showing some advantages. This antibody yielded positive staining in 370 of 425 (87%) scorable GIST, whereas CD117 was positive in 317 of 428 (74%) GIST and CD34 in 254 of 430 (59%) GIST. In GIST with mutations in PDGFRA, 79% (23/29) showed DOG1.1 immunoreactivity while only 9% (3/32) and 27% (9/33) stained for CD117 and CD34, respectively. Only 1 of 326 (0.3%) leiomyosarcomas and 1 of 39 (2.5%) synovial sarcomas among the 935 soft tissue tumors examined showed positive immunostaining for DOG1.1. In addition, DOG1.1 immunoreactivity was seen in fewer cases of carcinoma, melanoma, and seminoma as compared with KIT.

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    • "Recently, one of which was focused on the most important marker is DOG1. In the study of Espinosa et al in 425 cases they showed that DOG1 has a high specificity and sensitivity in the diagnosis of GIST and DOG1 positivity was 87% and 74% positiveness for c-kit [4]. West et al, they studied on 149 cases and showed that DOG1 positivity was 97.8%, the c-kit positivity was 94% in GIST [5] in the study of Miettinen et al at 1168 GIST cases DOG1 positivity was 94.8%, the c-kit positivity was 94.9%. "
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    ABSTRACT: Gastrointestinal stromal tumor is the most common mesenchymal neoplasia in the gastrointestinal tract and has a broad spectrum of pathological patterns and also clinical features changing from benign to malignant. Although the well-characterized parameters to predict the outcome have been the size and the mitotic index of the tumor in the patients with early-staged disease, bulky recurrent or metastatic tumor, resistance to medical treatment and mutation analysis are the prognostic factors for advanced stage-GIST. The aim of this study is to investigate new and more practical tissue markers, such as DOG1 and Ki-67 to specify the GIST diagnosis and also to predict the outcome in GIST patients with both localized and advanced staged disease.
    International Journal of Clinical and Experimental Medicine 01/2014; 7(7):1914-22. · 1.42 Impact Factor
    • "GISTs are believed to originate from the interstitial cells of Cajal (ICCs), the pacemaker cells of the intestine [8] [9]. GIST cells and ICCs share several characteristics, e.g. the highly specific markers CD117 and DOG1 [10] [11]. ICCs are functionally well characterized, though data for GISTs are scarce. "
    Cancer Research 08/2013; 73(8 Supplement):5317-5317. DOI:10.1158/1538-7445.AM2013-5317 · 9.28 Impact Factor
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    • "Before the discovery of TMEM16A as a CaCC, it was in fact already known to oncologists by various names— discovered on gastrointestinal stromal tumors protein 1 (DOG-1), oral cancer overexpressed 2 (ORAOV2), and tumor-amplified and overexpressed sequence 2 (TAOS- 2)— because of its high expression levels in some tumors, including gastrointestinal stromal tumors (GIST) (West et al., 2004; Espinosa et al., 2008), oral and esophageal squamous cell carcinoma (Huang et al., 2006; Kashyap et al., 2009). It has been suggested to serve as a hallmark for GIST, although its function in tumor biology is unknown. "
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    ABSTRACT: Calcium-activated chloride channels (CaCCs) are widely expressed in various tissues and implicated in physiological processes such as sensory transduction, epithelial secretion, and smooth muscle contraction. Transmembrane proteins with unknown function 16 (TMEM16A) has recently been identified as a major component of CaCCs. Detailed molecular analysis of TMEM16A will be needed to understand its structure-function relationships. The role this channel plays in physiological systems remains to be established and is currently a subject of intense investigation.
    Pharmacological reviews 11/2011; 64(1):1-15. DOI:10.1124/pr.111.005009 · 18.55 Impact Factor
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