Significance of vascular endothelial growth factor expression and its correlation with inducible nitric oxide synthase in gastric cancer

Abstract

AIM:To investigate the clinical significance of the expression of VEGF 165 mRNA and the correlation with vascular endothelial growth factor (VEGF) protein and inducible nitric oxide synthase (iNO) in human gastric cancer. METHODS:We tested VEGF 165 mRNA expression in 31 cases of resected gastric cancer specimens and normal paired gastric mucosae by RT-PCR. Total RNA was extracted with TRIzol reagents, transcribed into cDNA with oligo (dT 15 ) priming, inner controlled with β-actin expression and agarose gel isolated after PCR. VEGF expression was quantitated with IS1000 imaging system. Meanwhile we also examined expression levels of VEGF protein and iNOS in 85 cases of gastric cancer. All paraffin-embedded samples were immunohistochemically stained by streptavidin -peroxidase method (SP). RESULTS:The mean expression of VEGF 165 mRNA in gastric cancer was 1.125±0.356, significantly higher than that of normal paired mucosae, which was 0.760±0.278. Th e dat a ind ica te d t ha t t he ex pr ess ion l eve l of VEGF 165 mRNA was well related to lymph node metastasis and TNM stages of UICC. The expression levels in patients with lymph node metastasis and without lymph node metastasis were 1.219±0.377 and 0.927±0.205 respectively (P<0.05). The expression in stages I, II, III, IV was 0.934±0.194, 1.262±0.386 respectively (P<0.01). Further analysis showed the lymph node metastasis rate in the group with over-expression of VEGF was higher than that in the group with low expression of VEGF (83.3% vs 46.2%), and the ratio of stage III+IV in the group with overexpression of VEGF was also higher than that in the group with low expression with VEGF (77.8% vs 33.8%) (P<0.05). The positive rates of expression of VEGF protein and iNOS in 85 cases of gastric cancer were 75.4% and 58.8% respectively, and 50.1% of the patients showed positive staining both for iNOS and VEGF, the correlation with the two factors was significant (P=0.018). But more intensive analysis showed the immunoreactive grades of VEGF were not associated with that of iNOS. CONCLUSIONS:The expression of VEGF 165 mRNA is well related with lymph node metastasis and TNM stages of UICC in gastric cancer, and is concerned with the invasiveness and metastasis of gastric cancer. The relationship can be observed between the expression of VEGF and iNOS in gastric cancer.Song ZY, Wen SQ, Peng JP, Huang X, Qian KD. Significance of vascular endothelial growth factor expression and its correlation with inducible nitric oxide synthase in gastric cancer.

HIF-1α and VEGF are Associated with Disease Progression in Esophageal Carcinoma

“…In this study, VEGF expression tended to associate with iNOS immunoreactivity. These findings are in line with reports of Song et al In gastric cancer, they reported a correlation between VEGF and iNOS, and VEGF expression was related to TNM stages [44].…”

Inducible Nitric Oxide Synthase in the Carcinogenesis of Gastrointestinal Cancers

“…Zhang et al showed that in over 50% of gastric cancer patients, increased NOS2 expression was associated with elevated rates of lymph node metastasis, vascular invasion, distant metastasis, and tumor node metastasis stage (197). Moreover, NOS2 is also associated with increased density of intratumor microvessels and angiogenesis in gastric cancer (67,161). In addition, NOS2 has been shown to be positively correlated to lymphangiogenesis and lymphatic metastasis in gastric cancer (82).…”

Kallikrein-binding protein inhibits growth of gastric carcinoma by reducing vascular endothelial growth factor production and angiogenesis

“…VEGF and h-actin expression in serial sections were determined by immunostaining using monoclonal antibodies against VEGF and h-actin (1:100, Santa Cruz Biotechnology). VEGF staining was scored semiquantitatively as Song's method with minor modification (24). Briefly, the shade of staining was assigned to 0 to 3 scores according to staining density, and the percentage of staining cell was also assigned to 0 to 3 scores according to the percentage of positive staining cells.…”