*Article* **Canine Gastric Carcinomas: A Histopathological and Immunohistochemical Study and Similarities with the Human Counterpart**

**Alexandros Hardas 1,\*, Alejandro Suárez-Bonnet 1, Sam Beck 2, William E. Becker 1, Gustavo A. Ramírez 3 and Simon L. Priestnall 1**



**Simple Summary:** Gastric carcinoma (GC) continues to be one of the leading causes of death in humans and is the most common neoplasm in the stomachs of dogs. In both species, previous studies have demonstrated that the disease is heterogeneous, with genetic and environmental factors playing a quintessential role in disease pathogenesis. Compared to humans, the incidence of gastric carcinoma in dogs is low although, in a small number of breeds, a higher incidence has been reported. In dogs, the etiology and molecular pathways involved remain largely unknown. This retrospective study reviews current signalment data, evaluates the inflammatory component and association with *Helicobacter* spp. presence in various canine gastric carcinoma histological subtypes, and investigates potential molecular pathways involved in one of the largest study cohorts to date. The benefit of such a comparative study is to highlight the parallel histological features and molecular pathways between dogs and humans.

**Abstract:** Canine gastric carcinoma (CGC) affects both sexes in relatively equal proportions, with a mean age of nine years, and the highest frequency in Staffordshire bull terriers. The most common histological subtype in 149 CGC cases was the undifferentiated carcinoma. CGCs were associated with increased chronic inflammation parameters and a greater chronic inflammatory score when *Helicobacter* spp. were present. Understanding the molecular pathways of gastric carcinoma is challenging. All markers showed variable expression for each subtype. Expression of the cell cycle regulator 14-3-3σ was positive in undifferentiated, tubular and papillary carcinomas. This demonstrates that 14-3-3σ could serve as an immunohistochemical marker in routine diagnosis and that mucinous, papillary and signet-ring cell (SRC) carcinomas follow a 14-3-3σ independent pathway. p16, another cell cycle regulator, showed increased expression in mucinous and SRC carcinomas. Expression of the adhesion molecules E-cadherin and CD44 appear context-dependent, with switching within tumor emboli potentially playing an important role in tumor cell survival, during invasion and metastasis. Within neoplastic emboli, acinar structures lacked expression of all markers, suggesting an independent molecular pathway that requires further investigation. These findings demonstrate similarities and differences between dogs and humans, albeit further clinicopathological data and molecular analysis are required.

**Keywords:** canine; stomach; gastric carcinoma; *Helicobacter* spp.; p16; 14-3-3σ; E-cadherin and CD44
