The Expression Pattern of UDP-N-Acetyl-α-D-Galactosamine-Polypeptide N-Acetyl-Galactosaminyl Transferase-3 in Squamous Cell Carcinoma of the Esophagus

Abstract

Objective: UDP-N-acetyl-α-D-galactosamine-polypeptide N-acetylgalactosaminyl transferase-3 (GalNAc-T3) regulates the initial glycosylation of mucin-type O-linked proteins. Although a different expression of GalNAc-T3 has been reported in various cancers, the expression has not been characterized in squamous cell carcinoma (SCC) of the esophagus. Methods: We have also evaluated the expression of this enzyme in surgically resected esophageal mucosa. By immunohistochemical staining using a specific antibody, we evaluated the expression of GalNAc-T3 in 66 esophageal SCC and 28 dysplasia samples, and analyzed the relationship between the expression of GalNAc-T3 and clinicopathological features. Results: GalNAc-T3 was positively detected in the majority of the cases of SCC, but not in dysplasia as well as the normal counterparts in resected esophagus. GalNAc-T3 was determined to be positive in 37 cases (68.5%) of differentiated carcinomas, but only in 4 cases (33.3%) of undifferentiated carcinomas (p < 0.05). Hematogeneous metastasis was observed in 13 of 41 (31.7%) GalNAc-T3-positive tumors, which was significantly more frequent than in negative tumors (2/25, 8%; p < 0.05). The number of metastatic nodes was significantly higher in tumors with GalNAc-T3-positive than GalNAc-negative expression (4.2 ± 3.2 vs. 2.8 ± 1.3, p < 0.05). The survival rate tended to be lower for patients with GalNAc-T3-positive tumors, although the difference was not statistically significant (p = 0.18). Conclusion: GalNAc-T3 may play a positive role in the process of carcinogenesis and progression in esophageal SCC. Functional inhibition of GalNAc-T3 may be effective for the prevention and treatment of esophageal SCC.