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

## TL;DR

This study examines DOG1 protein expression in normal and cancerous dog tissues, finding it is not exclusive to gastrointestinal stromal tumors (GISTs) and could be relevant for other canine cancers.

## Contribution

The study is the first to comprehensively characterize DOG1 expression in a wide range of canine tissues and tumors.

## Key findings

- DOG1 is strongly expressed in multiple normal canine cell types beyond interstitial cells of Cajal.
- DOG1 shows high sensitivity in canine GISTs, slightly lower than KIT, but combining both markers improves diagnosis.
- Several non-GIST tumors also show strong DOG1 expression, suggesting broader relevance in canine malignancies.

## Abstract

A wide range of normal and neoplastic canine tissue samples were analyzed by immunohistochemistry in order to characterize the expression, distribution, and cellular localization of DOG1, the diagnostic marker for gastrointestinal stromal tumors (GISTs) in human pathology. Strong DOG1 immunoexpression was observed in several normal cell types other than interstitial cells of Cajal, including ovarian, testicular, thyroid, renal, salivary gland, and perivascular cells, partially similar to human expression patterns. Among canine tumors, DOG1 exhibited in GISTs a high diagnostic sensitivity, slightly lower than KIT, with results that highlight the diagnostic benefit of combining both markers. Notably, several spindle cell tumors and a fair number of carcinomas showed DOG1 levels comparable to those of GISTs, provided that DOG1 expression extends beyond GISTs and could have potentially significant implications also for additional canine malignancies.

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 (n = 55) and neoplastic canine tissues (n = 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.