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  • Title: Diagnostic significance of DOG-1 and PKC-θ expression and c-Kit/PDGFRA mutations in gastrointestinal stromal tumours.
    Author: Wang C, Jin MS, Zou YB, Gao JN, Li XB, Peng F, Wang HY, Wu ZD, Wang YP, Duan XM.
    Journal: Scand J Gastroenterol; 2013 Sep; 48(9):1055-65. PubMed ID: 23862765.
    Abstract:
    OBJECTIVE: To investigate discovered on gastrointestinal stromal tumor (GIST)-1 (DOG-1) and protein kinase C-θ (PKC-θ) expression in a series of GISTs and determine the sensitivity, specificity, and diagnostic value of these two antigens. METHODS: Immnunohistochemistry (IHC) was used to detect CD117, DOG-1, PKC-θ, CD34, Ki-67, α-smooth muscle actin (SMA), S100, and Desmin expression in 147 GISTs and 51 non-GISTs. c-Kit gene (exons 9, 11, 13, and 17) and platelet-derived growth factor receptor-alpha (PDGFRA) gene (exons 12 and 18) mutations were also detected. RESULTS: About 94.5% GISTs were CD117 positive, 96% were DOG-1 positive, and 90.5% were PKC-θ positive. DOG-1 had a specificity of 100%, while CD117 and PKC-θ had a specificity of 90% and 80%, respectively. There was no significant difference between DOG-1 and PKC-θ expressions when compared to CD117 expression. In 30 out of 42 (71.5%) GISTs, a c-Kit gene mutation was found, and in 3 out of 42 cases (7%), PDGFRA was mutated. Wild-type c-Kit/PDGFRA genes accounted for 21.5% (9/42). Most c-Kit gene mutations were found to be located at exon 11, mainly as in-frame deletions. Mutations in exon 9 were all missense mutations. Most PDGFRA gene mutations were found in exon 18, codon 842. c-Kit gene mutations in exons 13 and 17, and the PDGFRA gene mutation in exon 12 were not detected. CONCLUSIONS: Compared to CD117, DOG-1 is a biomarker with higher sensitivity and specificity. The combination of CD117 and DOG-1 can be used to improve the diagnosis of GIST. Although PKC-θ has a lower specificity than DOG-1, it can be a useful biomarker, especially in CD117(-) and/or DOG-1(-) cases.
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