Expression of inducible nitric oxide synthase is significantly correlated with expression of vascular endothelial growth factor and dendritic cell infiltration in patients with advanced gastric carcinoma.
OBJECTIVE
Nitric oxide (NO) is a product of L-arginine to L-citrulline conversion by nitric oxide synthase (NOS). The inducible form of NOS (iNOS) is one of three classes of NOS and the strongest producer of NO. It has been reported that NO correlates with angiogenesis and immune responses in some types of cancer, however, the correlations between iNOS expression, angiogenesis, and immune responses are still unclear in gastric carcinoma.


METHODS
iNOS expression was determined in 135 gastric cancer patients by immunohistochemical procedures and compared with the expression of vascular endothelial growth factor (VEGF), microvessel (MV) density, and dendritic cell (DC) infiltration to evaluate the effect of iNOS on angiogenesis and immune responses in gastric carcinoma.


RESULTS
iNOS expression was detected in 106 (78.5%) of 135 cases. There was a close correlation between iNOS expression and VEGF expression, a correlation with MV density and an inverse correlation with DC infiltration. There was no correlation between iNOS and p53 expression. The prognoses of patients whose tumors expressed iNOS were significantly worse than those of patients whose tumors did not express iNOS. Multivariate analysis indicated iNOS expression was an independent prognostic factor.


CONCLUSIONS
iNOS might be associated with tumor progression by stimulating angiogenesis and suppressing immune responses in gastric carcinoma.
Yamaguchi
Kenichi
K
Department of Surgery, Division of Surgical Oncology, Tottori University School of Medicine, Yonago, Japan.
Saito
Hiroaki
H
Oro
Shotaro
S
Tatebe
Shigeru
S
Ikeguchi
Masahide
M
Tsujitani
Shunichi
S
D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009389:Neovascularization, Pathologic; D019001:Nitric Oxide Synthase / Q000276:immunology / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D013274:Stomach Neoplasms / Q000098:blood supply / Q000276:immunology* / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000276:immunology / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II