Inducible nitric oxide synthase expression in benign and malignant cutaneous melanocytic lesions

Nitric oxide (NO) is synthesized by nitric oxide synthases (NOS) and plays an important role in tumour growth. In this study, inducible NOS (iNOS) exp ression was evaluated by immunohistochemistry in 34 melanocytic naevi (13 c ommon melanocytic naevi, six Spitz naevi, and 15 so-called 'dysplastic naev i'), ten cutaneous melanomas in situ, 50 stage I invasive melanomas, and ei ght subcutaneous metastases of melanoma, In addition, four samples of melan ocytic naevi and four samples of invasive melanomas were collected in order to perform western blot and northern blot analysis. By immunohistochemistr y, melanocytic naevi never expressed iNOS. Among cases of melanoma in situ, two were negative, seven displayed staining in less than 20% of melanoma c ells, and positivity was observed in 21-50% of melanoma cells in only one c ase. iNOS expression was detected in 46 out of 50 invasive melanomas (92%), Among these cases, 18 showed positivity in less than 20% of melanoma cells , 18 showed positivity in 21-50% of melanoma cells, and ten showed iNOS exp ression in more than 50% of cells. Statistical analysis revealed a signific ant difference in iNOS expression between melanocytic naevi and cutaneous m elanomas (p < 0.001), In addition, iNOS expression was significantly higher in invasive melanomas than in melanomas in situ (p=0,01), Among primary cu taneous melanomas, no significant correlation was found between iNOS expres sion and histopathological parameters (histotype, level, thickness and pres ence of regression/inflammatory infiltrate) and disease-specific survival. In subcutaneous melanoma metastases, iNOS expression was diffuse in more th an 50% of cells. Statistical analysis revealed that subcutaneous melanoma m etastases showed greater iNOS immunoreactivity than invasive melanomas (p = 0,02), Molecular analyses confirmed that iNOS mRNA and protein were highly expressed in melanoma samples. In conclusion, iNOS was constantly absent i n melanocytic naevi, whereas it was frequently expressed in melanomas, with up-regulation of the enzyme paralleling tumour progression, These data sug gest that iNOS may play a role in the malignant transformation of melanocyt es and in tumour growth. In addition, iNOS may be useful as an immunohistoc hemical marker for malignant melanocytic lesions. Copyright (C) 2001 John W hey & Sons, Ltd.