Clinical Significance Of Expression Of Inducible Nitric Oxide Synthase In Non-Small Cell Lung Cancer

ObjectiveNitric oxide synthase (NOS) is the key enzyme of the nitric oxide ( NO) synthesis, which is classified into constitutive nitric oxide synthase ( cNOS) and inducible nitric oxide synthase (iNOS) by its existing forms, and then cNOS is further classified into neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase ( eNOS). Those isoforms are named NOS1 NOS2 NOS3 in cloned time order,which are equivalent to nNOS,iNOS,eNOS respectively. The constitutive isforms of NOS, eNOS and nNOS, are calcium dependent and generate low levels of NO. In contrast to the constitutive NOS isforms, iNOS produces high NO levels;the activity of iNOS is calcium independent and largely regulated at the level of synthesis and mRNA and protein. A number of agents up - regulated iNOS,most notably lipopolysaccharides,inflammatory cytokines. Some investigations at home or abroad suggest that the effect of iNOS to tumor is two -way,either promotion or inhibition. Nowadays,there are few studies on the relationship between positive expression and Non - Small Cell lung cancer ( NSCLC ). Furthermore, the results of these studies are relatively different. In addition, there is no investigation involving the prognosis of those patients who had a positive iNOS expression. To clarify the clinical significance of iNOS positive expression may be helpful to the diagnosis, treatment and predicting outcome of those patients sufferring from lung cancer. Therefore, we plan to investigate the relation between the expression levels of the iNOS and TNM stage, histologi-cal lung cancer types, lymph node status, and the tumor status T in our study. Furthermore, we could evaluate how it affected the prognosis of the postoperativepatients with NSCLC.MethodsWe select 50 patients with NSCLC in the first clinical college of China Medical University ( CMU) and their surgically resected speciments of paraffin embedded from Jan 1999 to Dec 2000. We observed the expression of iNOS in those speciments immunohistochemically. According to the classification of lung cancer of WHO in 1999, those speciments is divided into three groups: squamous cell carcinoma, adenocarcinoma, large cell carinoma. We select the TNM and T stage in accordance with the TNM staging system of UICC in 1997. Follow - up visits on all patients were carried out from the day of operation to the end of 2000 by phone. Statistically, we compared the rate of positive expression of different groups classified by histological lung cancer types, TNM stages, T stages, and lymph node metastasis. In the meantime, the survival time of both positive patients and negative ones were analyzed.SPSS 13.0 was used for statistical analysis. Chi -square test was used for iNOS expression difference between groups, and Kaplan - Meier survival curve was used for survival rates comparison;log - rank test for survival curve comparison. Significance level was a =0.05.ResultsThere was positive expression in NSCLC. The expression of iNOS has a correlation with lymph node status ( P <0. 05). There was no significant difference between positive expression of iNOS and histological lung cancer types, TNM stages, T stages (P >0.05). But the data suggest that a direct correlation with expression of iNOS and clinical outcome ( P <0.05) .ConclusionPositive expression of iNOS was observed in NSCLC, which correlated withpostoperative survival time and lymph node status . Although iNOS level has no significant relation with T stage, we find the positive rate of T2 stage is much higher than that of Tl stage.The result suggests that positive expression of iNOS is related to bad clinical outcome because of promoting tumor growth and metastasis .