Expression of GalNAc-T3 and its relationships with clinicopathological factors in 61 extrahepatic bile duct carcinomas analyzed using stepwise sections—Special reference to its association with lymph node metastases—

Abstract

Extrahepatic bile duct carcinomas (EBDCs) still result in an unfavorable prognostic outcome, and little is known about their biological aggressiveness. Recently, UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyl transferase-3 (GalNAc-T3) was reported to be associated with differentiation and malignant potential of human carcinomas. Here, we investigated 61 EBDCs for their detailed clinicopathological features and GalNAc-T3 expression by immunohistochemistry, and then evaluated the relationships between the clinicopathological features and GalNAc-T3 expression patterns. Most of the EBDCs were massively invasive tumors with frequent vascular or perineural invasion and lymph node metastases. GalNAc-T3 expression was detected in all 61 EBDCs, and the expression patterns could be classified into granular and diffuse types. All four noninvasive or minimally invasive EBDCs were the granular type. Among the 58 minimally or massively invasive EBDCs, the GalNAc-T3 expression pattern at the luminal surface was the granular type in 38 cases (66%) and diffuse type in 20 cases (34%), while the expression pattern at the invasive front was the granular type in 26 cases (45%) and diffuse type in 32 cases (55%). Among the 38 cases with granular-type expression at the luminal surface, 26 cases (68%) remained the granular type and 12 cases (32%) became the diffuse type at the invasive front. All 20 cases with diffuse-type expression at the luminal surface remained the diffuse type at the invasive front. Diffuse-type GalNAc-T3 expression at the invasive front was significantly associated with lymph node metastasis (Po0.05). There were no significant correlations between the GalNAc-T3 expression patterns and other clinicopathological factors, including tumor differentiation, depth of invasion or overall survival. In conclusion, EBDCs alter their GalNAc-T3 expression pattern during tumor growth, and the difference in the GalNAc-T3 expression pattern may be associated with lymph node metastasis. Clinically, preoperative evaluation of GalNAc-T3 expression is considered to be useful for decisions regarding operative procedures.

Expression of UDP-N-acetyl-D-galactosamine: Polypeptide N-acetylgalactosaminyltransferase-6 in Gastric Mucosa, Intestinal Metaplasia, and Gastric Carcinoma

“…In addition, our results also showed a particular association of venous invasion with ppGalNAc-T6 expression in tumors localized in the body region of the stomach. Different levels of ppGalNAc-T3 have been detected in patients with various types of carcinomas (Shibao et al 2002;Gu et al 2004;Ishikawa et al 2004;Miyahara et al 2004;Yamamoto et al 2004;Landers et al 2005;Inoue et al 2007), and this has been associated with a poor prognosis. ppGalNAc-T6 exhibits a high sequence homology to ppGalNAc-T3, and in vitro studies have shown that both enzymes display similar acceptor substrate specificities (Bennett et al 1999b).…”

N-Acetylgalactosaminyltransferase-14 as a potential biomarker for breast cancer by immunohistochemistry

“…Higher expression of GalNAc-T1, GalNAc-T2 and GalNAc-T3 has also been described in colorectal carcinoma when compared with the normal colonic epithelium [27]. Different levels of expression of GalNAc-T3 were detected in patients with colorectal [12], lung [28], pancreatic [29], gastric [30], gallbladder [31], prostate [32] and extrahepatic bile duct carcinomas [33], and it was identified as an independent factor of prognosis. GalNAc-T6, which exhibits a high sequence homology to GalNAc-T3, has been recently described to be expressed in most ductal breast carcinomas but not in normal breast epithelium.…”

De novo expression of human polypeptide N-acetylgalactosaminyltransferase 6 (GalNAc-T6) in colon adenocarcinoma inhibits the differentiation of colonic epithelium

“…GalNAc-T3 and GalNAc-T6 display high similarity at both DNA and amino acid levels, having similar genomic organization with nine identically positioned intron/exon boundaries in the coding regions (10). GalNAc-T3 is expressed in almost all normal epithelia, and dysregulated expression of GalNAc-T3 has been observed in various carcinomas, including oral (41,47), colon (44), pancreatic (48 -50), breast (51), gallbladder (52), gastric (53,54), prostate (55), renal (56), lung (57), esophageal (58), thyroid (59), and extrahepatic bile duct (42) carcinomas. GalNAc-T6 is also reported to be aberrantly expressed in various types of cancer, including breast (60 -64), gastric (40), renal (56), and pancreatic (49) carcinomas.…”