Positive expressions of N-acetylglucosaminyltransferase-V (GnT-V) and beta1-6 branching N-linked oligosaccharides in human testicular germ cells diminish during malignant transformation and progression.
N-acetylglucosaminyltransferase-V (GnT-V) is an enzyme that catalyzes beta1-6 branching of N-acetylglucosamine on asparagines (N)-linked oligosaccharides of cell proteins. We examined the implication of GnT-V and beta1-6 branching N-linked oligosaccharide expression in human testicular germ cells during malignant transformation and cancer progression. We analyzed immuhistochemically orchiectomy specimens of 130 patients with testicular germ cell tumors (TGCT) using anti-GnT-V monoclonal antibody, and compared GnT-V expression with clinicopathological features. N-linked oligosaccharide structural analysis was also performed to confirm the oligosaccharide profile produced by GnT-V. GnT-V was positive in all normal testis samples. This positive incidence declined in TGCT according to clinical stage; 16/71 (22.5%) in stage I, and 3/59 (5.1%) in stage II/III (p=0.015, chi(2) test). When divided into pathological subtypes, GnT-V positive incidences in stage I seminoma, stage II/III seminoma, stage I non-seminomatous germ cell tumor (NSGCT), and stage II/III NSGCT were 3/43 (7%), 0/22 (0%), 13/28 (46.4%), and 3/37 (8.1%), respectively. In stage I NSGCT, patients with GnT-V-negative tumor samples were at a significantly higher risk of recurrence than those with GnT-V-positive tumors (p=0.015, log-rank test). N-linked oligosaccharide structural analysis revealed that a normal testis has three kinds of beta1-6 branching N-linked oligosaccharides, all of which are downregulated in TGCT tissues. These results suggest that GnT-V and beta1-6 branching N-linked oligosaccharide expressions are downregulated during carcinogenesis and progression of human TGCT. GnT-V may be a promising recurrence predictor for stage I NSGCT.
Kyan
Atsushi
A
Department of Urology, Hirosaki University School of Medicine, Hirosaki 036-8562, Japan.
Kamimura
Noritaka
N
Hagisawa
Shigeru
S
Hatakeyama
Shingo
S
Koie
Takuya
T
Yoneyama
Takahiro
T
Arai
Yoichi
Y
Nakagawa
Hiroaki
H
Nishimura
Shin-Ichiro
S
Miyoshi
Eiji
E
Hashimoto
Yasuhiro
Y
Ohyama
Chikara
C
D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D015536:Down-Regulation; D006801:Humans; D008297:Male; D017351:N-Acetylglucosaminyltransferases / Q000032:analysis*; D009367:Neoplasm Staging; D009373:Neoplasms, Germ Cell and Embryonal / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D009844:Oligosaccharides / Q000032:analysis*; D013736:Testicular Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology
D009844:Oligosaccharides; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase