title: Inducible nitric oxide synthase expression in laryngeal neoplasia: correlation with angiogenesis.
abstract: 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.
authors.affiliation: Department of Human Pathology and Oncology, University of Florence, Viale G. B. Morgagni 85, 50134 Florence, Italy. Franchi@UNIFI.IT
authors.forename: Alessandro
authors.initials: A
authors.lastname: Franchi
authors.forename: Oreste
authors.initials: O
authors.lastname: Gallo
authors.forename: Milena
authors.initials: M
authors.lastname: Paglierani
authors.forename: Iacopo
authors.initials: I
authors.lastname: Sardi
authors.forename: Lucia
authors.initials: L
authors.lastname: Magnelli
authors.forename: Emanuela
authors.initials: E
authors.lastname: Masini
authors.forename: Marco
authors.initials: M
authors.lastname: Santucci
mesh_terms: 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
chemical_list: D014408:Biomarkers, Tumor; D019001:Nitric Oxide Synthase