Abstract
Simple SummaryGastric carcinoma (GC) is the second leading cause of death in humans and the most frequent malignancy in the stomach of dogs. As in humans, the prognosis of canine gastric cancer is generally poor owing to the advanced stage at the time of diagnosis, resulting in limited treatment options. In dogs, the molecular mechanisms involved in the growth and progression of gastric cancer remain largely unknown. Trefoil factor 1 (TFF1) protein is a mucin-associated secretory molecule that plays an important role in the maintenance and protection of epithelial surface integrity. Some human studies showed that TFF1 can protect mucosa against damage and suppress carcinogenesis, while other studies showed that TFF1 can restrict cell adhesion, promote tumor cell invasion, and block necrosis of tumor cells. In human gastric cancer, TFF1 has been found to decrease, and it has been proposed that it might act as a tumor suppressor factor. The present study was carried out to investigate whether there is a relationship between TFF1 and canine gastric carcinogenesis. We found an association between reduced expression of TFF1 and the development and progression of gastric cancer in dogs. The pathological and behavioral similarities between spontaneous canine GC and human counterparts make it logical to assume that dogs may be a useful model for human gastric cancer.TFF1 expression is markedly reduced in human GCs, suggesting that TFF1 is a tumor suppressor for human gastric cancer. The present study evaluated the expression and distribution pattern of TFF1 in paraffin-embedded canine gastric tissue samples, including normal mucosa (n = 3), polyps (n = 8), carcinomas (n = 31) and their adjacent non-neoplastic mucosa (n = 30), neoplastic emboli (n = 14), and metastatic lesions (n = 9), by immunohistochemistry (IHC). All normal gastric tissues expressed TFF1 in the superficial foveolar epithelium and mucopeptic cells of the neck region. Most gastric polyps (GPs) displayed immunoreactivity for TFF1 in >75% of the epithelial component. In GCs, the expression of TFF1 was found reduced in 74.2% of the cases. The level of TFF1 expression had a decreased tendency from normal gastric mucosa to GPs and GCs (p < 0.05). No significant differences in the expression of TFF1 were found in GCs, according to age, sex, histological type based on World Health Organization (WHO) and Lauren classification, tumor location, depth of tumor invasion, presence of neoplastic emboli or metastatic lesions. The median survival time of GC patients with preserved and reduced TFF1 immunoexpression were 30 and 12 days, respectively. Kaplan–Meier analysis revealed no significant survival differences between the two groups (p > 0.05). These findings suggest that TFF1 protein may play a role in canine gastric carcinogenesis, and further studies are necessary to define its usefulness as a prognostic indicator in canine gastric carcinoma.
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