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OBJECTIVE To explore the expression of inducible nitric oxide synthase(iNOS), p53 and bcl-2 in gastric precancerous and cancerous lesions and to examine the expression of these proteins in relation to clinical features.METHODS The expressions of iNOS, p53 and bcl-2 proteins in gastric precancerous and cancerous lesions and their correlations with the clinical features were determined using immunohistochemical assays (Power VisionTM two-step method) on 84 gastric carcinomas and 54 gastric atypical hyperplastic tissues. Apoptotic cells were evaluated by terminal deoxynucleotidyl transferase- mediated dUTP-biotin nick-end labeling (TUNEL).RESULTS Expression of iNOS, p53 and bcl-2 was significantly higher in gastric carcinoma (GC) tissues than in gastric atypical hyperplastic tissues. Among the 84 carcinomas, the expression of p53 was observed in 50 (59.52%), bcl-2 in 43 (51.19%), and iNOS in 65 (77.58%). Overexpression of iNOS and bcl-2 in gastrlc carcinoma was related to tumor size and iNOS was related to the presence of lymph node metastasis (P<0.05). The expression of proteins did not correlate with age, sex, stage of disease, or differentiation. Expression of iNOS in gastric carcinoma tissues was positively correlated with bcl-2 expression (χ2=8.926, P=0.003),and also with p53 expression (χ2= 5.2430, P= 0.022). The mean apoptotic indexes (Al) were 1.29%±0.50 in low-grade atypical hyperplasia (LG),0.96%±0.36 in high-grade atypical hyperplasia (HG) and 0.70%±0.43 in GC, with the difference being significant between LG, HG and GC (P<0.05). There was a significant positive correlation between iNOS expression and the Al in GC (t=3.0815, P=0.0028).CONCLUSION iNOS was expressed in the majority of gastric carcinoma tissues and correlated with cellular apoptosis associated with p53 and bcl-2 expression. iNOS overexpression is closely associated with p53 and bcl-2 accumulation status. iNOS may play a synergistic role in the pathogenesis of GC.