DOG1 is a sensitive and specific immunohistochemical marker for diagnosis of canine gastrointestinal stromal tumors

Dailey, Deanna D.; Ehrhart, E. J.; Duval, Dawn L.; Bass, Todd A.; Powers, Barbara E.

doi:10.1177/1040638715578878

Cited by 38 publications

(50 citation statements)

References 51 publications

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“…The presence of discovered‐on‐GIST 1 (DOG1), a calcium‐dependent chloride channel important in the generation of ICCs' “slow waves,” has been determined to ubiquitously define GIST in humans, regardless of c‐Kit expression . Although previous publications have defined GISTs in dogs as mesenchymal intestinal neoplasms expressing c‐Kit, recent literature suggests that a combination of c‐Kit and DOG1 IHC is most sensitive for diagnosis of GISTs in dogs …”

Section: Introductionmentioning

confidence: 99%

Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of gastrointestinal stromal tumors of dogs

Berger

Johannes

Jergens

et al. 2018

Veterinary Internal Medicne

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BackgroundGastrointestinal stromal tumors (GISTs) are uncommon intestinal neoplasms in the dog. Literature regarding adjunctive therapy for GISTs in dogs is sparse. High‐risk GISTs in humans respond to tyrosine kinase inhibition in the adjuvant setting.ObjectivesTo review cases of toceranib phosphate use in dogs with GISTs and provide initial assessment of possible biological activity. A secondary aim was to evaluate patient and tumor characteristics for possible prognostic value.AnimalsTwenty‐seven dogs with confirmed GISTs based on histopathology and immunohistochemistry treated with toceranib.MethodsRetrospective study in which cases of toceranib use in dogs with GIST were solicited using the American College of Veterinary Internal Medicine Oncology and Small Animal Internal Medicine listservs.ResultsFive of 7 dogs with gross disease experienced clinical benefit (71%; 3 complete responses, 1 partial response, 1 stable disease). These included 2 dogs with durable responses after toceranib discontinuation. Median progression‐free interval (PFI) in dogs with gross disease was 110 weeks (range, 36‐155 weeks). Median PFI in dogs with microscopic disease was 67 weeks (range, 9‐257 weeks). Metastasis at diagnosis (P = 0.04) and high mitotic index (P < 0.001) were associated with shorter PFI in toceranib‐treated dogs.Conclusions and Clinical ImportanceBiological activity of toceranib is evident in dogs with gross disease. Metastasis of GIST at diagnosis, as well as high tumor mitotic index, was associated with shorter PFI in toceranib‐treated dogs. Larger studies are needed to define postsurgical risk and refine the use of toceranib in dogs with gross and microscopic GIST.

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Section: Introductionmentioning

confidence: 99%

Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of gastrointestinal stromal tumors of dogs

Berger

Johannes

Jergens

et al. 2018

Veterinary Internal Medicne

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“…GISTs are believed to originate from the interstitial Cajal cells (ICC) in normal bowel wall or from precursors of these cells [2]. Recently, anoctamin 1, calcium activated chloride channel (ANO1) previously called DOG1 (Discovered On Gastrointestinal tumor protein 1), was found widely expressed in GIST, even in c-KIT negative tumors, and has been shown as a sensitive and specific immunohistochemical marker for GIST [3, 4]. …”

Section: Introductionmentioning

confidence: 99%

Circulating tumor cells as a prognostic and predictive marker in gastrointestinal stromal tumors: a prospective study

Zhi

Zhou

et al. 2016

Oncotarget

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BackgroundCirculating tumor cells (CTC) are prognostic and predictive for several cancer types. Only limited data exist regarding prognostic or predictive impact of CTC on gastrointestinal stromal tumor (GIST) patients. The aim of our study was to elucidate the role of CTC in GIST patients.ResultsA total of 121 GIST patients and 54 non-GIST samples were enrolled in the study. The cutoff value for ANO1 positive was 3*10−5 and 65 (54%) GIST patients were defined as ANO1 positive. ANO1s were more frequently detected in unresectable patients. Tumor size, mitotic count and risk level were associated with ANO1 detection in resectable GIST patients. The presence of ANO1 significantly correlated with poor disease-free survival (15.3 versus 19.6 months, p = 0.038). Most patients turned ANO1-negative after surgery and inversely, all 21 patients with recurrence turned ANO1-positive with high ANO1 expression levels. Moreover, in the neoadjuvant setting, decline of ANO1 expression level correlated with the response of imatinib.MethodsCells from peripheral blood mononuclear cells tested positive for anoctamin 1, calcium activated chloride channel, ANO1 (DOG1) were considered as tumor CTC of GISTs. The expression levels of ANO1 were determined using quantitative real-time polymerase chain reaction (qRT-PCR). The highest level of ANO1 expression in non-GIST samples was used as the “cutoff” value.ConclusionANO1 detection by qRT-PCR in peripheral blood is of clinical potential for monitoring recurrence and evaluating therapeutic efficacy of imatinib for GIST patients.

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“…It is worth mentioning that, more recently, the DOG1 antibody has been suggested as a more sensitive marker for the diagnosis of GIST (especially in c-kit-negative cases). DOG1 is a plasma membrane protein that is involved in the transport of chlorine [6].…”

Section: Discussionmentioning

confidence: 99%

Gastrointestinal Stromal Tumor Associated with Hypertrophic Osteopathy in a Dog

Veiga

Baetas

Nassif

et al. 2019

Acta Scientiae. Vet.

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Background:Gastrointestinal stromal tumor (GIST) is a malignant mesenchymal neoplasm rarely described in the veterinary routine. The aim of this study was to report a case of GIST accompanied by a periosteal reaction, suggestive of hypertrophic osteopathy, in a dog. Case: An 11-year-old male dog had a history of progressive weight loss, difficulty in locomotion, and dyspnea. During clinical care, increased bone volume was observed. Blood samples were collected for a complete blood count and biochemical analysis. The dog also underwent thoracic radiography and abdominal ultrasonography. The test results revealed anemia, leukocytosis, hypocalcemia, hypoalbuminemia, and hypocholesterolemia. The radiographic images of the limbs showed a generalized periosteal reaction, and thoracic radiography indicated changes compatible with mild chronic lung disease. Ultrasonographic findings indicated a neoformation in the intestinal loop of the right mesogastric region and increased volume in the left testicle, both of which were indicative of neoplasia. Therefore, the dog was referred for surgery, wherein the intestinal mass and both testes were removed; the intestinal mass and left testicle were subjected to histopathological diagnosis. The results of the biopsies confirmed that the testicular neoplasm was a seminoma, whereas the intestinal nodule was compatible with GIST, and immunohistochemical analysis was necessary to confirm the diagnosis. On the basis of positive labeling for the antibodies vimentin, desmin, S100, and c-kit, the diagnosis of GIST was confirmed. Therefore, the animal underwent metronomic chemotherapy with 12 mg/m 2 cyclophosphamide every 24 h for 3 months, and thereafter every 48 h for 6 months. Moreover, the dog was periodically monitored via imaging (radiography of the anterior and posterior limbs, abdominal ultrasonography, and computed tomography). A few months after the surgical resection of the intestinal nodule, radiography revealed that the periosteal reactions had disappeared, but ultrasonography revealed nonspecific alterations of mild thickening and enlargement of the intestinal loops. Computed tomography revealed two nodular areas of soft-tissue attenuation in the right mesogastric region. Although the possibility of tumor recurrence was raised, the animal's owner chose only to perform palliative treatment. After 4 months, ultrasonography revealed a neoformation in the right mesogastric region. On July 29, 2018 the animal had a worsening of its clinical condiction, with tumor recurrence by ultrasound exam. The owners didn´t accept returning to the oncologist and made an option for a conservative treatment with tramadol (3 mg/kg/TID), dipirone (25 mg/kg/TID), and vitaminic supplement based on docosahexaenoic acid plus eicosapentaenoic acid (30 mg/kg, once daily). On August, 28, 2018 he was euthanized. The dog's postsurgical survival time was 15 months. Discussion: The dog described in the present report was large and elderly, both of which are predisposing factors for GIST development. Although...

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DOG1 is a sensitive and specific immunohistochemical marker for diagnosis of canine gastrointestinal stromal tumors

Cited by 38 publications

References 51 publications

Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of gastrointestinal stromal tumors of dogs

Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of gastrointestinal stromal tumors of dogs

Circulating tumor cells as a prognostic and predictive marker in gastrointestinal stromal tumors: a prospective study

Gastrointestinal Stromal Tumor Associated with Hypertrophic Osteopathy in a Dog

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