Expression of N-acetylglucosaminyltransferase v is associated with prognosis and histology in non-small cell lung cancers.
OBJECTIVE
N-Acetylglucosaminyltransferase V (GnT-V), a key enzyme in the formation of branching of asparagine-linked oligosaccharides, is strongly linked to tumor invasion and metastasis of colon and breast cancers. However, GnT-V is expressed in many tissues, including normal lung. GnT-V expression has not been examined previously in human lung cancers. The objective of this study is to examine GnT-V expression in non-small cell lung cancers (NSCLCs) and to determine its relationship to biological and clinicopathological characteristics and prognosis.


METHODS
GnT-V expression was studied by immunohistochemistry in 217 surgically resected NSCLCs and analyzed statistically in relation to various characteristics.


RESULTS
High GnT-V expression was found in 113 (52.1%) NSCLCs, and low GnT-V expression was found in 104 (47.9%) NSCLCs. Multivariate logistic regression analysis revealed a significant association between low GnT-V expression and squamous cell carcinomas, as compared with nonsquamous cell carcinomas (P = 0.02). Among biological characteristics of tumors, Ki-67 labeling index was higher in tumors with low GnT-V expression than in those with high GnT-V expression, although this difference was not statistically significant (P = 0.09). Patients with tumors having low GnT-V expression had significantly shorter survival time than patients with tumors having high GnT-V expression in 103 patients with pStage I NSCLCs (5-year survival rates, 49% and 86%, respectively; P = 0.0009), as well as in 59 patients with pStage I non-squamous cell carcinomas (5-year survival rates, 54% and 89%, respectively; P = 0.007). Low GnT-V expression was a significant unfavorable prognostic factor in pStage I NSCLCs (hazard ratio, 2.86; P = 0.002) and in pStage I nonsquamous cell carcinomas (hazard ratio, 3.02; P = 0.02). Furthermore, beta1-6 branching of asparagine-linked oligosaccharides, which are products of GnT-V, were increased highly or moderately in 8 of 10 tumors with high GnT-V expression, as judged by leukoagglutinating phytohemagglutinin staining.


CONCLUSIONS
GnT-V expression is associated with histology in NSCLCs. Low GnT-V expression is associated with shorter survival and poor prognosis in pStage I overall NSCLCs and non-squamous cell carcinomas.
Dosaka-Akita
Hirotoshi
H
Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. hdakita@med.hokudai.ac.jp
Miyoshi
Eiji
E
Suzuki
Osamu
O
Itoh
Tomoo
T
Katoh
Hiroyuki
H
Taniguchi
Naoyuki
N
D000368:Aged; D001980:Bronchi / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016017:Odds Ratio; D010835:Phytohemagglutinins / Q000032:analysis; D011379:Prognosis; D012016:Reference Values; D020545:Respiratory Mucosa / Q000201:enzymology; D012307:Risk Factors; D012907:Smoking; D016019:Survival Analysis; D013997:Time Factors
D010835:Phytohemagglutinins; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase