Diagnostic Relevance of Overexpressions of PKC-θ and DOG-1 and KIT/PDGFRA Gene Mutations in Extragastrointestinal Stromal Tumors: A Korean Six-Centers Study of 28 Cases

Background: We investigated the clinicopatho- logical and immunohistochemical characteristics, genetic aberrations and prognostic factors in 28 patients with extragastrointestinal stromal tumors (EGISTs) from six centers in South Korea. Patients and Methods: Immunohistochemistry was performed for c-KIT (CD117), PKC-θ (protein kinase C theta), DOG-1 (discovered on GIST-1), CD34, alpha-smooth muscle actin (α-SMA), vimentin, desmin and S-100 protein. Genetic analyses for the KIT gene (exon 9, 11, 13 and 17) and the platelet- derived growth factor receptor alpha (PDGFRA) gene (exons 12 and 18) were performed by direct sequencing of PCR products. The relationships of various clinicopathological characteristics and outcomes were also examined. Results: Of the tumor samples, 78.6% (22/28) were located in the intra- abdominal cavity including the omentum and mesentery, and 10.7% (3/28) were located in the retroperitoneum. All patients were older than 39 years. The median size of the tumors was 10 cm for the maximum diameter. When first detected, 57.1% of EGISTs were large in size, measuring more than 10 cm. Tumors that were larger than 10 cm were found more frequently among tumors with more than 10 mitoses per 50 high-power fields (HPFs) and this finding was statistically significant (p 10/50 HPFs). Overall survival (OS) was correlated with tumor size >10 cm, tumor necrosis, obvious nuclear atypia, mitotic counts >10/50 HPFs and epithelioid or mixed cell type (p<0.05). Eleven EGISTs (44.0%) had mutations in the KIT gene and 6 (24.0%) had mutations in the PDGFRA gene, the