Cyclooxygenase-2 (COX-2): first immunohistochemical marker distinguishing early cutaneous melanomas from benign melanocytic skin tumours

Abstract

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.

Different expression of cyclooxygenase-2 (COX-2) in selected nonmelanocytic human cutaneous lesions

“…In this work, and in our earlier studies of COX-2 in melanocytic cutaneous lesions and in adjacent skin [31,32], we have consistently observed in a large number of samples of normal human skin positive staining of keratinocytes of the granular and spinous layers. Our present study demonstrated that papillomas, verrucas and normal skin express COX-2 at comparable levels.…”

“…Our studies have demonstrated that the development and progression of human cutaneous melanoma are accompanied by a clear increase of COX-2 expression in melanocytes [31,32]. It should be noted that earlier data on COX-2 expression in 382 382 382 382 382 [33].…”

NFAT signalling is a novel target of oncogenic BRAF in metastatic melanoma

“…Recent clinical trials of the specific COX-2 inhibitor celecoxib suggest that COX-2 inhibition may increase the clinical efficacy of temozolomide for melanoma treatment (Gogas et al, 2006). Furthermore, as COX-2 is more highly expressed in cutaneous melanoma and metastatic melanoma compared with benign naevi (Chwirot and Kuzbicki, 2007), defining upstream regulators could be valuable for drug development. Pertinent to cancer pathogenesis and metastasis, c-myc and VEGF are additional transcriptional targets of NFAT (Buchholz and Ellenrieder, 2007), further emphasising the relevance of NFAT signalling for melanoma therapy.…”

“…Furthermore, accumulating evidence suggests that increased NFAT transcriptional activity contributes to both the development and progression of cancer (Buchholz and Ellenrieder, 2007), and identifies NFAT signalling as a potential target for cancer therapy. In the context of melanoma, increased expression of the NFAT target gene cyclooxygenase-2 (COX-2), an inducible enzyme involved in the conversion of arachidonic acid to prostaglandins, correlates with poor prognosis (Kuzbicki et al, 2006;Chwirot and Kuzbicki, 2007), suggesting that NFAT signalling may be important in melanoma. However, upstream activators of COX-2 in melanoma and a role for oncogene-driven NFAT activation remain undefined.…”

Biomarkers for Melanoma Diagnosis and the Technologies Used to Identify Them

“…It has been suggested that GPC3 may be a useful early stage biomarker for patients with the early stages of the disease (0 -II) (Nakatsura et al, 2004;Ikuta et al, 2005). Moreover, cyclooxygenase-2 (COX-2) (Chwirot and Kuźbicki, 2007), serum amyloid A (SAA) (Mian et al, 2005;Findeisen et al, 2009) and DNA methylation profiling (Conway et al, 2011) can be used to distinguish between early melanomas and benign nevi.…”