Differential Expression of Nitric Oxide Synthase Isotypes in Advanced Human Gastric Carcinoma and Its Relationship to H. pylori Infection

초록

It has been reported that nitric oxide sunthase (NOS) isotypes are present in human tumor cell lines and solid tumor tissues. The expression and cellular localization of 3 isotypes of NOS was detected in 79 advanced gastric carcinoma tissues together with adjacent normal mucosa. Endothelial NOD (eNOS) revealed immunoreactivity mainly in the endothelial cells and some mucosal epithelial cells. Neuronal NOS (nNOS) revealed immunoreactivity mainly in the nerve fibers and the base of the foveolar epithelial cells. Most of the normal gastric mucosa cells did not reveal iNOS, however, inflammatory cells and the cells showing intestinal metaplasia revealed strong immunoreactivity. Fourty seven (59.4%), 65(79.71%), 59(74.68%) of 79 cases revealed eNOS, nNOS, and iNOS expression, respectively. Sonstitutive (endothelial and neuronal) NOS showed lower activity in the cancer cells than normal mucosal cells whereas inducible NOS showed higher activity in the cancer cells. Intestinal type adenocarcinoma tended to have higher activity of eNOS (p=0.001) and nNOS(p=0.005) than diffuse type adenocarcinoma. The eNOS(p=0.001) and nNOS(p=0.022) tended to be highly expressed when the tumor was differentiated. Tumor larger than 5cm tended to have hight activity of nNOS than tumors smaller than 5cm in diameter(p=0.017). The NOS expression and other clinicopathological parameters including lymphovascular invasion, perineural invasion, depth of invasion, and lymph node metastasis did not show significant relationship. The coexistence of H.pylori in the adjacent normal mucosa was correlated with iNOS expression (p=0.011) but not with eNOS or nNOS expression. These results suggest that all three isotypes of NOS have been implicated in gastric carcinoma development, however, contribute differentiality to the gastric carcinogenesis and progression and especially the iNOS which might have been induced by H. pylori organisms has a different role from the consitutive NOS.