The expression pattern of UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetyl-galactosaminyl transferase-3 in squamous cell carcinoma of the esophagus.
OBJECTIVE
UDP-N-acetyl-alpha-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).


CONCLUSIONS
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.
Ishikawa
Makoto
M
Department of Surgery, Division of Surgical Oncology, University of Tokyo, Tokyo, Japan. makoto-ishi@umin.ac.jp
Kitayama
Joji
J
Kohno
Kimitoshi
K
Nagawa
Hirokazu
H
D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D004947:Esophagus / Q000201:enzymology / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D017350:N-Acetylgalactosaminyltransferases / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009367:Neoplasm Staging; D016019:Survival Analysis; D015996:Survival Rate; D000097763:Polypeptide N-acetylgalactosaminyltransferase
D017350:N-Acetylgalactosaminyltransferases; D009363:Neoplasm Proteins; D000097763:Polypeptide N-acetylgalactosaminyltransferase