Expression of UDP-N-acetyl-α-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. Cancer 2002;94:1939–46. © 2002 American Cancer Society. DOI 10.1002/cncr.10423