Inducible nitric oxide synthase expression in various laryngeal lesions in relation to carcinogenesis, angiogenesis, and patients' prognosis

• Published in: Acta oto-laryngologica 2007-01, Vol.127 (9), p.970-979
• Main Authors: Shigyo, Hiroshi, Nonaka, Satoshi, Katada, Akihiro, Bandoh, Nobuyuki, Ogino, Takeshi, Katayama, Akihiro, Takahara, Miki, Hayashi, Tatsuya, Harabuchi, Yasuaki
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; angiogenesis; Biological and medical sciences; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; Disease-Free Survival; Female; Humans; inducible nitric oxide synthase (iNOS); Laryngeal Neoplasms - metabolism; Laryngeal Neoplasms - mortality; Laryngeal Neoplasms - pathology; Laryngeal squamous cell carcinoma; Lymphatic Metastasis; Male; Medical sciences; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local - metabolism; Neovascularization, Pathologic - metabolism; Nitric Oxide Synthase Type II - metabolism; Otorhinolaryngology. Stomatology; Precancerous Conditions - metabolism; Prognosis; prognostic factor; Tumor Suppressor Protein p53 - metabolism; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Vascular Endothelial Growth Factor A - metabolism; VEGF
• ISSN: 0001-6489; 1651-2251
• DOI: 10.1080/00016480601089382

Conclusions: The inducible nitric oxide synthase (iNOS) expression leading to vascular endothelial growth factor (VEGF) overexpression may be useful as a factor for predicting recurrence after initial treatment and prognosis in laryngeal squamous cell carcinoma (SCC). Objective: We analyzed expression of iNOS, p53, and VEGF in various laryngeal lesions. Materials and methods: The study samples consisted of 63 SCC, 20 dysplasia, 7 polyp, and 5 normal epithelium of the larynx. The expression of iNOS, p53, and VEGF was identified by immunohistological methods. Results: No positive immunostaining for iNOS, p53, and VEGF was observed in normal epithelium and polyps. In contrast, with the progression from mild/moderate dysplasia to severe dysplasia to carcinoma, their expression levels increased. In dysplasia, there was a significant positive correlation among expression of iNOS, p53, and VEGF. In SCC, iNOS expression correlated with VEGF overexpression and microvessel density, but not with p53 overexpression. In SCC, the expression of iNOS and VEGF significantly increased in patients who developed local recurrence and/or metastases after initial treatments. Kaplan-Meier analysis showed that disease-free survival was significantly shorter in patients with iNOS or VEGF expression. Multivariate analysis showed expression of iNOS and VEGF as independent indicators for poor disease-free survival.