Thymidine phosphorylase and cycloxygenase-2 expression in malignant melanoma

Background: Cyclooxygenase-2 (COX-2) protein expression has been described in melanoma and it seems to be associated with tumor progression and angiogenesis. Thymidine phosphorylase (TP) is a proangiogenic factor overexpressed in several human malignancies; it is also involved in the multistep process that converts the prodrug capecitabine into 5-fluorouracile. Both enzymes could be induced by several factors and could represent potential target for anticancer treatments. The aim of the study was to evaluate COX-2 and TP expression in a cohort of primary malignant melanomas and to investigate the correlation between these enzymes and known prognostic factors. Methods: Immunoistochemical TP and COX-2 expression was evaluated in 35 consecutive paraffin-embedded samples of cutaneous melanoma diagnosed between 1999 and 2003. Pathologic features were reviewed by expert pathologists. Clinical data were retrieved from medical charts. TP and COX-2 mRNA expression and protein expression was evaluated in melanoma cell lines through RT-PCR and Western Blot. Results: TP and COX-2 were highly expressed in 11 and 11 cases, respectively. High TP expression was associated with 1 mm melanoma (p = 0.0005) and Clark levels I-III (p = 0.017). High COX-2 expression was significantly associated with decreased disease free survival in multivariate analyses (p= 0.029). No significant association between these two biomarkers and other classical prognostic features was evident; a marginal association between COX-2 expression and mitotic rate > 0/mm2 was evident (p = 0.06). TP expression in melanoma cell lines was low; conversely, COX-2 was differently expressed among cell lines. Conclusions: The present study showed an interesting association between TP expression and thin malignant melanoma. In addition, COX-2 expression resulted to be associated with worse outcome. Further molecular characterizations of this series of melanoma is ongoing. The potential role of TP and COX-2 as therapeutic targets in melanoma deserves further investigations