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


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.
Shigyo
Hiroshi
H
Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical College, Japan.
Nonaka
Satoshi
S
Katada
Akihiro
A
Bandoh
Nobuyuki
N
Ogino
Takeshi
T
Katayama
Akihiro
A
Takahara
Miki
M
Hayashi
Tatsuya
T
Harabuchi
Yasuaki
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007822:Laryngeal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D052247:Nitric Oxide Synthase Type II