To clarify the clinicopathological characteristics of adenocarcinoma of the gastric cardia (AGC), including its association with Barrett’s esophagus and intestinal metaplasia, 49 surgically resected early AGCs (EAGCs) were examined clinicopathologically, histopathologically, histochemically, and immunohistochemically. The clinicopathological characteristics of the patients with EAGC were compared with those of 293 patients with early adenocarcinoma of the distal stomach (EADS) and 7 patients with early adenocarcinoma of the esophagus (EAE). Histochemical staining with paradoxical concanavalin A (ConA) and immunohistochemical staining with monoclonal antibodies 45M1, Ccp58, and 56C6 were performed to investigate the differentiation phenotype of the tumor. ConA and 45M1 were used for markers of the gastric phenotype, and Ccp58 and 56C6 were used for markers of the intestinal phenotype. EAGC was associated with a higher mean age (p < 0.0001), a higher male-to-female ratio (p < 0.05), a higher incidence of elevated-type tumors (p < 0.0001), a higher incidence of differentiated-type tumors (p < 0.0001), and greater depth of invasion (p < 0.05) compared with EADS. EAE was associated with a higher incidence of elevated-type tumors (p < 0.001), a higher incidence of differentiated-type tumors (p < 0.05), and larger tumor size (p < 0.05) compared with EADS. The prevalence of Barrett’s esophagus in patients with EAGC was significantly lower than in patients with EAE (10.2%, 5/49 patients vs. 100%, 7/7; p < 0.0001). The prevalence of intestinal (Barrett’s) metaplasia in surrounding non-neoplastic mucosa in patients with EAGC was significantly lower than in patients with EADS or EAE (36.7%, 18/49 patients vs. 72.0%, 211/293 and 85.7%, 6/7; p < 0.0001 and p < 0.05, respectively). EAGC was associated with a higher incidence of tumors that reacted positively for gastric phenotype markers alone than EADS (32.7%, 16/49 cases vs. 17.1%, 50/293; p < 0.05) and a lower incidence of tumors that reacted positively for both gastric and intestinal markers than EADS or EAE (40.8%, 20/49 cases vs. 59.7%, 175/293 and 85.7%, 6/7; p < 0.05, respectively). Our findings indicate that AGC forms a specific category different from both adenocarcinoma of the distal stomach and esophagus in terms of association with Barrett’s esophagus or intestinal metaplasia, and the differentiation phenotype of the tumor.

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