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Abstract
BackgroundLymphatic metastasis is the most important parameter in the spread of gastric carcinomas. Nitric oxide (NO) is a signaling molecule that plays an important role in inflammation and carcinogenesis. In this study, the possible link between inducible nitric oxide synthase (iNOS) expression with lymphangiogenesis and the clinicopathological parameters of gastric carcinomas was investigated.MethodsIn this study, iNOS expression and D2-40 (lymphatic endothelium-specific marker monoclonal antibody) reactivity were examined immunohistochemically in 41 gastric adenocarcinoma and 20 non-neoplastic gastric tissues. iNOS expression was scored semiquantitatively in the tumor parenchyma and stroma. D2-40-positive lymphatic vessels were used in the determination of lymphatic invasion and intratumoral and peritumoral lymphatic vascular density.ResultsiNOS expression was higher in gastric carcinoma tissue compared with non-neoplastic tissue. Particularly, iNOS expression in tumor cells was found to be closely related to lymphangiogenesis and lymphatic metastasis. The density of lymphatic invasion as well as intratumoral and peritumoral lymphatic vascular density were positively correlated with lymph node metastasis.ConclusionsOur results suggest that iNOS-mediated NO formation plays an important role in gastric carcinogenesis, tumor lymphangiogenesis, and the development of lymphatic metastases. Inhibition of the NO pathway may be an alternative treatment of gastric carcinomas.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1713572940104388.
Highlights
Lymphatic metastasis is the most important parameter in the spread of gastric carcinomas
Our study demonstrated that both Intratumoral lymphatic vascular density (I-lymphatic vascular density (LVD)) and peritumoral LVD (P-LVD) were positively correlated with lymphatic invasion (LI), Lymphatic invasion density (LID), the presence of lymph node metastasis, and the number of metastatic lymph nodes
We identified a significant correlation between inducible nitric oxide synthase (iNOS) expression in tumor cells and inflammation density, loss of differentiation, and parameters related to lymphatic tumor spread/lymphangiogenesis
Summary
Lymphatic metastasis is the most important parameter in the spread of gastric carcinomas. The possible link between inducible nitric oxide synthase (iNOS) expression with lymphangiogenesis and the clinicopathological parameters of gastric carcinomas was investigated. The most important factors in the initiation and progression of angiogenesis are nitric oxide (NO) and the vascular endothelial growth factor (VEGF) family. NO exists in various cell types and is synthesized from L-arginine by the nitric oxide synthase (NOS) enzyme family. Studies have shown that NO plays an important role in tumor lymphangiogenesis and lymphatic metastasis. Studies of head and neck squamous cell carcinoma have shown that the NOS activity of tumor cells is closely associated with lymphangiogenesis and lymph node metastasis [8]
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