Clinicopathological study of fractional exhaled nitric oxide dynamics and intratumoral inducible nitric oxide synthase expression in primary lung cancer patients.

Background: Inducible nitric oxide synthase (iNOS) is expressed in non-small cell lung cancer (NSCLC) tumor cells and contributes to tumorigenesis. Nitric oxide, an indicator of airway inflammation, is concurrently produced in the airway epithelium. However, the interrelationships and predictive importance of iNOS remain unclear. This study aimed to investigate whether iNOS could serve as a novel biomarker for NSCLC. Methods: Immunohistochemical analysis of iNOS expression in the tumor cells of 101 consecutive patients with NSCLC undergoing lung resection was conducted. The fractional exhaled nitric oxide (FeNO) levels were evaluated pre- and postoperatively using a clinically applied respiratory function testing device. iNOS expression was assessed by immunochemical staining for expression within tumor cells. Results: iNOS expression in the tumor cells was significantly associated with squamous cell carcinoma (P<0.01). No significant correlation between the FeNO levels and iNOS expression scores existed; however, the FeNO levels in positive cases of squamous cell carcinoma were significantly higher than those in negative cases (P<0.01). The FeNO levels did not decrease in the iNOS-negative cases after tumor resection in the squamous cell carcinoma group but were significantly lower in the positive cases (P=0.03). Conclusions: iNOS expression in tumor cells showed a characteristic tendency toward squamous cell carcinoma, suggesting its potential for FeNO-mediated localization and diagnosing lung cancer.