Expression of UDP-N-acetyl-alpha-D-galactosamine-polypeptide galNAc N-acetylgalactosaminyl transferase-3 in relation to differentiation and prognosis in patients with colorectal carcinoma.
BACKGROUND
Tumor development usually is accompanied by alterations of O-glycosylation. Initial glycosylation of mucin-type, O-linked proteins is catalyzed by one of the UDP-GalNAc-polypeptide N-acetyl-galactosaminyl transferases, such as GalNAc-T3, which is expressed in adenocarcinoma cells. The authors investigated whether such expression influenced tumor differentiation or prognosis in patients with colorectal carcinoma.


METHODS
The expression of GalNAc-T3 was evaluated immunohistochemically in 106 paraffin embedded samples from surgically resected colorectal carcinomas and was related to patient and tumor characteristics. Western blot analysis was performed on seven samples of frozen tissue.


RESULTS
Strong tumor expression of GalNAc-T3 predicted 5-year survival in patients with colorectal carcinoma (67.2% vs. 43.6% for weak expression; P = 0.017). GalNAc-T3 expression was not associated with age, gender, tumor size, tumor location, or disease stage but was related to histologic differentiation (P = 0.049) and depth of invasion (P = 0.031). Univariate analysis showed that strong GalNAc-T3 expression significantly enhanced the likelihood of survival. Multivariate Cox survival analysis identified enzyme expression as an independent prognostic factor that was second only to TNM stage.


CONCLUSIONS
GalNAc-T3 expression is a novel and useful indicator of tumor differentiation, disease aggressiveness, and prognosis in patients with colorectal carcinoma.
Shibao
Kazunori
K
Department of Surgery I, University of Occupational and Environmental Health, School of Medicine, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu 807-8555, Japan.
Izumi
Hiroto
H
Nakayama
Yoshifumi
Y
Ohta
Ryo
R
Nagata
Naoki
N
Nomoto
Minoru
M
Matsuo
Ken-ichi
K
Yamada
Yuji
Y
Kitazato
Kenji
K
Itoh
Hideaki
H
Kohno
Kimitoshi
K
D000230:Adenocarcinoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002454:Cell Differentiation; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000201:enzymology / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000201:enzymology; D017350:N-Acetylgalactosaminyltransferases / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D000097763:Polypeptide N-acetylgalactosaminyltransferase
D017350:N-Acetylgalactosaminyltransferases; D000097763:Polypeptide N-acetylgalactosaminyltransferase