Cyclooxygenase-2 (COX-2) is an enzyme that plays an important role in the production of prostaglandins. Numerous studies have demonstrated increased levels of COX-2 in human cancers of different types. It is thought that COX-2 may be involved in the development and progression of malignant tumours. However, data on the changes in COX-2 expression during the development and progression of human melanoma are relatively limited. Moreover, the results reported by different groups disagree to a large extent. The aim of this work was to evaluate whether COX-2 protein might be considered a potential molecular marker of melanoma progression. The expression of COX-2 was determined immunohistochemically in formalin-fixed, paraffin-embedded specimens of 64 human melanocytic skin tumours (17 naevi, 36 primary cutaneous melanomas and 11 lymph node melanoma metastases, with six pairs of primary and metastatic lesions obtained from the same patients). It was found that the expression level of COX-2 was dependent on both the stage and histopathological type of the melanoma. Collectively, our data indicate that changes in the expression level of COX-2 are correlated with the development and progression of human melanoma, and imply that the COX-2 protein may be considered a potential prognostic and predictive marker in malignant melanoma.

We have reported recently that changes in expression level of COX-2 are correlated with development and progression of human melanoma. In this study, we investigated whether the COX-2 expression level might be a useful immunohistochemical marker for distinguishing cutaneous melanomas from benign melanocytic lesions. Up to now, immunohistochemical markers have not ensured satisfactory sensitivity and specificity of differential pathologic diagnosis of melanoma. The expression of COX-2 was determined immunohistochemically in formalin-fixed, paraffin-embedded specimens of 33 early Clark I/II melanomas and 58 naevi. Mean COX-2 expression in melanomas was significantly stronger than in naevi (P approximately 10(-13)). A simple diagnostic algorithm using threshold values of the COX-2 expression level allows for differentiation between early melanomas and naevi with high sensitivity (Se) and specificity (Sp) (for Se between 91 and 100%, Sp values change between 96.5 and 51.7%). Areas under the receiver operating characteristic curves were, respectively, 0.97+/-0.02 and 0.86+/-0.04 for the COX-2 expression in central and border regions of the lesions. For all the melanomas (not only the early ones),the respective areas under the ROC curve values were 0.98+/-0.01 and 0.97+/-0.02. In conclusion, COX-2 is the first immunohistochemical marker that allows the distinguishing of early melanomas from benign melanocytic lesions with both high sensitivity and specificity.