DOG1 Immunohistochemical Expression in Normal and Neoplastic Canine Tissues: Is It Only a Marker for GISTs?

Abstract

DOG1 is a transmembrane protein highly expressed in human GISTs. In dogs, DOG1 has been studied to a limited extent in GISTs, where its diagnostic value is considered comparable to KIT, while its expression in other canine tissues remains uncharacterized. The aim of this study is to assess the expression of DOG1 in canine normal and neoplastic tissues, with particular emphasis on a large cohort of GISTs to verify their diagnostic role in comparison with KIT. To achieve this, we analyzed a total of 143 FFPE samples of normal (<i>n</i> = 55) and neoplastic canine tissues (<i>n</i> = 88) by immunohistochemistry. DOG1 was strongly expressed in several cell types, with distribution and intensity patterns that partially overlap those reported in humans. In canine GISTs, DOG1 showed strong and widespread reactivity with a sensitivity slightly inferior to KIT (92% vs. 96%); however, one intestinal mesenchymal tumor KIT-negative/DOG1-positive highlights the importance of combining both markers to maximize the correct diagnosis. Moderate to strong immunohistochemistry for DOG1 has been found in several other tumors, sometimes comparable to that of GISTs. This suggests that DOG1 should not be associated exclusively with GISTs and may provide a basis for further investigation into the role of DOG1 in canine malignancy.