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Increased expression of inducible nitric oxide synthase for human oral submucous fibrosis, verrucous hyperplasia, and verrucous carcinoma.

Three isoforms of nitric oxide synthase (NOS), endothelial, neuronal and inducible NOS (iNOS), have been identified in humans. Enhanced expression of iNOS protein has been previously reported for human oral epithelial dysplasias, a human oral premalignant epithelial lesion; however, this expression has not been demonstrated for other premalignant epithelial lesions, namely, oral submucous fibrosis (SF) and verrucous hyperplasia (VH). On the other hand, iNOS protein expression has not been reported in human oral verrucous carcinoma (VCa). The aim of this current study was to determine whether iNOS protein also occurs for oral SF, VH and VCa lesions. We found that membranous stainings were observed chiefly in oral SF lesions (17/20, 85%), whereas cytoplasmic stainings were mainly found in the VH variants (16/20, 80%). By contrast, cytoplasmic and/or nuclear stainings were observed in the specimens of verrucous carcinoma (17/20, 85%). Since no iNOS activity could be detected for any of our specimens of normal buccal mucosa in the present immunohistochemical study, this suggests that an NOS-dependent mechanism may be involved in the malignant transformation of these two premalignant oral epithelial lesions.