DOG1 antibody in the differential diagnosis of gastrointestinal stromal tumors: a study of 1840 cases.
ABSTRACT 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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ABSTRACT: To investigate the clinicopathologic features of patients with extra-gastrointestinal stromal tumors (EGISTs) in South Korea. A total of 51 patients with an EGIST were identified. The clinicopathologic features, including sex, age, location, tumor size, histology, mitotic rate, immunohistochemical features, genetic status and survival data, were analyzed. The median age was 55 years (range: 29-80 years), and male:female ratio was 1:1.04. The most common site was in the mesentery (n = 15) followed by the retroperitoneum (n = 13) and omentum (n = 8). The median tumor size was 9.0 cm (range: 2.6-30.0 cm) and the median mitotic rate was 5.0/50HPF. (1/50 - 185/50). KIT was analyzed in 16, which revealed 10 cases with wild-type KIT and 6 cases with an exon 11 mutation. Among 51 patients, 31 patients had undergone surgery, and 10 had unresectable disease and had taken palliative imatinib, which resulted in 22.7 mo of progression-free survival. Of the patients who had undergone surgery, 18 did not take adjuvant imatinib, and 8 of these were categorized as "high risk" according to the risk criteria. However, the relapse-free survival was not different (P = 0.157) between two groups. Because the biologic behaviors of GISTs differ according to the location of the tumor, a more stratified strategy is required for managing EGISTs including incorporation of molecular features.
Archives of pathology & laboratory medicine 03/2015; DOI:10.5858/arpa.2014-0578-CP · 2.88 Impact Factor
Zeitschrift für Gastroenterologie 08/2012; 50(08). DOI:10.1055/s-0032-1324185 · 1.67 Impact Factor