N-acetylgalactosaminyl transferase-3 is a potential new marker for non-small cell lung cancers

Abstract

N-acetylgalactosaminyl transferase-3 (GalNAc-T3) is an enzyme involved in the initial glycosylation of mucin-type O-linked proteins. In the present study, we used immunohistochemistry to examine GalNAc-T3 expression in 215 surgically resected non-small cell lung cancers. We analysed the biological and clinical importance of GalNAc-T3 expression, especially with regard to its potential as a prognostic factor. We found that normal bronchial epithelial cells, bronchial gland cells, and alveolar pneumocytes showed cytoplasmic immunostaining for GalNAc-T3. Low expression of GalNAc-T3, observed in 93 of 215 tumours (43.4%), was found more frequently in tumours from smokers than those from nonsmokers (P=0.001), in squamous cell carcinomas than nonsquamous cell carcinomas (P50.0001), and in moderately and poorly differentiated tumours than well differentiated tumours (P=0.0002). Multivariate logistic regression analysis showed that an association of low GalNAc-T3 expression with squamous cell carcinomas was the only one significant relationship of GalNAc-T3 expression with various factors (P50.0001). Moreover, tumours losing GalNAc-T3 expression had a significantly higher Ki-67 labelling index than tumours retaining GalNAc-T3 expression (P=0.0003). Patients with low GalNAc-T3 expression survived a significantly shorter time than patients with high GalNAc-T3 expression in 103 pStage I non-small cell lung cancers (5-year survival rates, 58% and 78%, respectively; P=0.02 by log-rank test) as well as in 61 pStage I nonsquamous cell carcinomas (5-year survival rates, 63% and 85%, respectively; P=0.03). Low GalNAc-T3 expression was an unfavourable prognostic factor in pStage I non-small cell lung cancers (hazards ratio, 2.04; P=0.03), and in pStage I nonsquamous cell carcinomas (hazards ratio, 2.70; P=0.03). These results suggest that GalNAc-T3 is a new marker of non-small cell lung cancers with specificity for histology and prognosis.

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—

“…In the adenocarcinomas of some organs, including the pancreas and gallbladder, the presence of weak expression or diffuse-type GalNAc-T3 expression in EBDCs T Inoue et al localization of GalNAc-T3 was correlated with tumor aggressiveness. [24][25][26][27][28][29] On the other hand, early-stage gastric carcinomas with submucosal invasion tended to show positive (strong or granular) GalNAc-T3 expression, while early-stage undifferentiated gastric carcinomas showing positive GalNAc-T3 expression were associated with significantly higher frequencies of metastatic lymph node involvement. 30 In addition, GalNAc-T3-positive esophageal squamous cell carcinomas exhibited more aggressive behavior.…”

“…Although most previous studies evaluating GalNAc-T3 expression by immunohistochemistry have divided the observed expression patterns into high-intensity (strong, positive) and low-intensity (weak, negative) groups, [24][25][26][27][28]30,31 Miyahara et al 29 divided the GalNAc-T3 expression patterns of gallbladder carcinomas into granular and diffuse types, mostly corresponding to highintensity and low-intensity expression, respectively. We also found that the immunohistochemical staining of GalNAc-T3 in EBDCs showed granulartype and diffuse-type expression patterns, and these features of EBDCs were similar to those reported for gallbladder adenocarcinomas.…”

“…17,18 Furthermore, recent studies have suggested a relationship between GalNAc-T3 expression and the tumor differentiation or progression, including prognosis, of human adenocarcinomas in the colon, lung, stomach, pancreas and gallbladder. [24][25][26][27][28][29][30] Although the GalNAc-T subtypes are usually localized in the Golgi apparatus, their subcellular localization alters following malignant transformation due to reorganization of the Golgi apparatus elements. 8,19,20 Therefore, not only the levels but also the patterns of GalNAc-T3 expression, such as the subcellular distribution, may be associated with the malignant transformation and differentiation of adenocarcinoma cells.…”

Expression of N -Acetylglucosaminyltransferase V Is Associated with Prognosis and Histology in Non-Small Cell Lung Cancers

“…The labeled streptavidin biotin method was used on 4-m sections of formalin-fixed, paraffinembedded tissues after deparaffinization. The primary antibodies used were a mouse monoclonal MIB-1 antibody (Immunotech, Marseilles, France), a mouse monoclonal antihuman p27 KIP1 antibody (clone 1B4; Novocastra, Newcastle, United Kingdom), a mouse monoclonal antihuman cyclin E antibody (HE12; PharMingen, San Diego, CA), and a rabbit polyclonal antibody against a synthesized peptide of human GalNAc-T3 (21).…”

Mucin Glycosylating Enzyme GALNT2 Regulates the Malignant Character of Hepatocellular Carcinoma by Modifying the EGF Receptor

“…Risk of epithelial ovarian cancer (8) and coronary artery disease (9) have been associated with single nucleotide polymorphisms of GALNT1 and GALNT2, respectively. GALNT3 expression is a potential diagnostic marker for lung (10) and pancreatic (11) cancers. GALNT6 modifies mucin 1 glycosylation and regulates proliferation of breast cancer cells (12).…”