The diagnostic utility of DOG1 expression in KIT-negative GIST

Abstract

10551 Background: Accurate pathologic classification of GIST is mandatory in order to allow proper treatment. Approximately 5% of cases fail to express KIT (CD117) therefore representing a diagnostic challenge. DOG1 represents a novel marker originally identified in GIST by gene profiling analysis that potentially may prove helpful in recognizing KIT-negative GIST. Methods: 156 cases of GIST, 56 neural tumors, 66 smooth muscle tumors, 31 desmoid fibromatoses and 29 synovial sarcomas were retrieved from the files of the Departments of Pathology of Treviso General Hospital, of UCL, and of Stanmore Royal National Orthopaedic Hospital. All cases were immunostained for DOG1, KIT (CD117) and PKCtheta. The diagnosis in KIT negative GIST was further confirmed by mutational analysis of KIT and PDGFRA genes. Results: KIT was positive in 148/156 GIST and was negative in all non-GIST lesions. DOG1 positivity was present in 155/156 GIST. Weak and focal staining was observed in 2/31 desmoid fibromatoses and in 2/29 synovial sarcomas. Importantly, all KIT-negative cases were strongly DOG1 positive. PKCtheta immunopositivity was present in 149/156 GIST, in 1/55 neural tumors, in 30/66 smooth muscle tumors and in 19/29 synovial sarcomas. Conclusions: 1. KIT still represents the most specific immunohistochemical marker for GIST. 2. DOG1 represents both a sensitive and specific immunohistochemical marker for GIST. 3. DOG1 should be included in the routine diagnostic immunohistochemical panel as it allows proper classification of KIT-negative GIST. No significant financial relationships to disclose.