Expression of UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetylgalactosaminyltransferase isozyme 3 in the subserosal layer correlates with postsurgical survival of pathological tumor stage 2 carcinoma of the gallbladder.
OBJECTIVE
Little is known about the molecular events leading to the development and progression of pathological tumor stage 2 (pT(2)) gallbladder carcinoma. An alteration in the site of O-glycosylation may be associated with malignant behavior of carcinoma cells by modulation of the biological properties of the target mucin. The UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetylgalactosaminyltransferase isozyme 3 (GalNAc-T3) has the epithelial gland-specific expression and catalyzes mucin-type O-glycosylation. In this study, immunohistochemistry was performed to determine the expression level of GalNAc-T3 in 34 cases of pT(2) gallbladder carcinoma to determine the correlation of the GalNAc-T3 expression level with mode of recurrence and postsurgical survival.


RESULTS
The expression levels of GalNAc-T3 protein and mRNA were increased in gallbladder carcinomas compared with the levels in adjacent noncancerous tissues and in intact gallbladders. Immunostaining of GalNAc-T3 was recognized in the cancerous epithelia, and the subcellular localization was classified into granular and diffuse types. In the 34 cases of pT(2) carcinoma, the localization of GalNAc-T3 was granular type in 50% and diffuse type in 50% of the cases at the deepest invading sites in the subserosal layer. Postsurgical recurrence was significantly more frequent in cases showing diffuse-type localization of GalNAc-T3 at the deepest invading sites (65%) than in those showing granular-type localization (23%; P < 0.05). Postsurgical survival was significantly poorer in cases showing diffuse-type localization than in those showing granular-type localization (P = 0.033)


CONCLUSIONS
In pT(2) gallbladder carcinoma, the presence of diffuse-type localization of GalNAc-T3 in the subserosal layer is correlated with aggressiveness of the disease. This phenotype may serve as a unique biological feature associated with the malignant behavior.
Miyahara
Naoki
N
Department of Cancer Biology and Molecular Immunology, Faculty of Pharmaceutical Sciences, The University of Tokyo, Tokyo.
Shoda
Junichi
J
Kawamoto
Toru
T
Furukawa
Masato
M
Ueda
Tetsuya
T
Todoroki
Takeshi
T
Tanaka
Naomi
N
Matsuo
Kenichi
K
Yamada
Yuji
Y
Kohno
Kimitoshi
K
Irimura
Tatsuro
T
D015415:Biomarkers / Q000032:analysis; D002277:Carcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000601:surgery*; D006801:Humans; D008297:Male; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D016019:Survival Analysis; D000097763:Polypeptide N-acetylgalactosaminyltransferase
D015415:Biomarkers; D017350:N-Acetylgalactosaminyltransferases; D009363:Neoplasm Proteins; D000097763:Polypeptide N-acetylgalactosaminyltransferase