The Novel Carbohydrate Tumor Antigen C2-O-sLex Is Upregulated in Canine Gastric Carcinomas

Abstract

Sialyl Lewis x–modified core 2 branched O-glycans (C2-O-sLex) on human leukocytes mediate much higher-affinity adhesion to selectins on activated vascular endothelium than does sialyl Lewis x on other structures. In some canine and human carcinomas, high expression of sLex-decorated carbohydrates has been associated with metastasis and, in humans, a poor prognosis, but detection in canine gastric carcinomas is unreported. The authors hypothesized that these carbohydrates are highly expressed in more malignant types of canine gastric carcinomas, they promote metastasis, and they are associated with a poorer prognosis for dogs. The objectives were to determine the presence and importance of C2-O-sLex expression in canine gastric carcinomas. Routine histological sections of 16 canine gastric carcinomas were categorized on the basis of 3 classification schemes: World Health Organization, Lauren, and Goseki. Serial sections were stained with antibodies directed against C2-O-sLex (CHO-131 monoclonal antibody), cytokeratin (Lu-5 monoclonal antibody), and stains to detect neutral and acid mucins (periodic acid–Schiff and alcian blue). Whereas normal gastric mucosal epithelial cells were negative for C2-O-sLex, 56% of the tumors examined were positive for C2-O-sLex. Importantly, the majority of more poorly differentiated tumor types had more numerous and larger intensely stained areas of C2-O-sLex expression compared with moderate to well-differentiated tumor types. Signet ring–type carcinomas had markedly higher distribution and intensity of periodic acid–Schiff and alcian blue staining than did tubular carcinomas. These findings suggest that C2-O-sLex is a tumor-associated antigen that may play a role in the invasiveness and metastatic potential of certain types of canine gastric carcinomas.