Inducible nitric oxide synthase expression in laryngeal neoplasia: correlation with angiogenesis.
BACKGROUND
The nitric oxide (NO) pathway plays a relevant role in angiogenesis and tumor progression in squamous cell carcinoma (SCC) of the head and neck. The aim of this study was to assess whether the NO pathway may be correlated with angiogenesis in the transition from laryngeal dysplasia to invasive carcinoma.


METHODS
We investigated the expression of the inducible NO synthase (iNOS) in 26 laryngeal precancerous lesions and 35 squamous cell carcinomas with respect to microvessel density. In addition, we determined iNOS activity and cGMP levels in specimens from SCCs.


RESULTS
There was a significant increase of iNOS levels detected immunohistochemically passing from hyperplastic/mild dysplastic to moderate/severe dysplastic lesions to SCC (p =.04). Accordingly, Northern and Western analyses demonstrated higher iNOS mRNA and protein levels in SCCs than dysplastic mucosa. iNOS expression was significantly correlated with microvessel counts both in the group of preneoplastic lesions (p =.02) and in the group of SCCs (p =.01). In addition, iNOS activity was correlated with iNOS immunohistochemical expression (p =.1) and was significantly associated with increased vascularization (p =.03) in SCCs. Similarly, iNOS expression was significantly correlated with cGMP levels in SCC (p =.02) and increased tumor vascularization correlated with higher cGMP levels (rs =.4; p =.01).


CONCLUSIONS
Our data indicate that the NO pathway may play a relevant role in the angiogenesis associated with the progression from laryngeal dysplasia to laryngeal SCC.
Franchi
Alessandro
A
Department of Human Pathology and Oncology, University of Florence, Viale G. B. Morgagni 85, 50134 Florence, Italy. Franchi@UNIFI.IT
Gallo
Oreste
O
Paglierani
Milena
M
Sardi
Iacopo
I
Magnelli
Lucia
L
Masini
Emanuela
E
Santucci
Marco
M
D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D001707:Biopsy, Needle; D015152:Blotting, Northern; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D046508:Culture Techniques; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000201:enzymology* / Q000473:pathology; D007830:Larynx / Q000098:blood supply; D008297:Male; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000201:enzymology* / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000378:metabolism*; D015588:Observer Variation; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000201:enzymology* / Q000473:pathology; D011336:Probability; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
D014408:Biomarkers, Tumor; D019001:Nitric Oxide Synthase