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

Abstract

Gastrointestinal stromal tumors (GISTs) and leiomyosarcomas are histologically similar primary neoplasms commonly occurring in the gastrointestinal tract of dogs and humans. Immunohistochemical staining (IHC) is needed to differentiate between these 2 entities and positive reactivity for KIT (cluster of differentiation [CD]117) is regarded as the gold standard for diagnosis of canine GIST. Studies estimate 5–10% of human GISTs stain negative or only weakly positive for KIT and have identified DOG1 (discovered on gastrointestinal stromal tumors protein 1) as a highly sensitive and specific marker for human GISTs. The purpose of this study was to evaluate immunoreactivity of a commercially available DOG1 antibody for use in diagnosis of canine GISTs. Fifty-five primary mesenchymal gastrointestinal tumors with histologic features consistent with GIST or leiomyosarcoma were evaluated via IHC for KIT, DOG1, and desmin. A subset of tumors was additionally evaluated for reactivity for smooth muscle actin (SMA). Thirty-three tumors (60%) were diagnosed as GIST based on positive immunoreactivity for KIT or DOG1 regardless of reactivity for desmin or SMA. Most GISTs (32/33, 97.0%) had similar staining for both KIT and DOG1. DOG1 expression was identified in 2 tumors (1 study tumor and 1 additional tumor) negative for KIT and desmin that had histologic features consistent with KIT-negative, platelet-derived growth factor receptor-alpha (PDGFRA)-mutant human GISTs. Our results suggest that DOG1 has improved specificity and sensitivity to that of KIT for differentiating between canine GISTs and leiomyosarcomas. Inclusion of both DOG1 and KIT IHC in diagnostic panels will improve the accuracy of canine GIST diagnosis.