Background: Although the incidence of adenocarcinoma of the stomach has decreased over the past several decades, gastric cardia carcinoma has increased over the same period.

Methods: The clinicopathologic characteristics and immunohistochemical staining results of 21 proteins were investigated in 165 patients with cardia carcinoma, including 74 patients with true cardia carcinoma and 91 patients with subcardia carcinoma, and the results were compared with the results from 564 patients with noncardia carcinoma.

Results: In the clinicopathologic analysis, patients who had cardia carcinoma tended to have tumors with poorly differentiated histology according to the World Health Organization classification system (P = 0.012), diffuse type according to the Lauren classification system (P = 0.049), and advanced pathologic TNM stage (P < 0.001). On immunohistochemical staining, loss of the p16 (P = 0.038) and smad4 (P < 0.001) tumor suppressor genes was more frequent in cardia carcinoma than in noncardia carcinoma. Carcinoembryonic antigen and CD44 overexpression were more frequent in patients with cardia carcinoma (P < 0.05). Conversely, patients who had cardia carcinoma exhibited less frequent expression of MUC1 (P = 0.008) and MUC5AC (P = 0.006) compared with patients who had noncardia carcinoma. Epstein-Barr virus infection was more common in patients with cardia carcinoma (P < 0.001). In the survival analysis, the patients with cardia carcinoma had a poorer prognosis. In the multivariate analysis, tumor location in the cardia was confirmed as an independent, poor prognostic factor in patients with gastric carcinoma.

Conclusion: Cardia carcinoma and noncardia carcinoma differed in their clinicopathologic characteristics and in their alterations of gene expression, as evaluated by immunohistochemistry. The current results support the hypothesis that cardia carcinoma forms a specific category of gastric carcinoma that is distinct from noncardia carcinoma.