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Kuzbicki L, Sarnecka A, Chwirot BWExpression of cyclooxygenase-2 in benign naevi and during human cutaneous melanoma progression. Melanoma Res 16:29-36

Department of Medical Biology, Institute of General and Molecular Biology, Nicolaus Copernicus University, Toruń, Poland.
Melanoma Research (Impact Factor: 2.28). 03/2006; 16(1):29-36. DOI: 10.1097/01.cmr.0000194430.77643.a0
Source: PubMed

ABSTRACT

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.

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    • "In a study of Becker et al. (2009), COX-2 was found in 95 % of melanoma revealing a significant correlation between immunohistochemical staining intensity and Breslow index. Kuzbicki et al. (2006) reported a coherency between COX-2 expression and development as well as progression of human melanoma. Thus, COX-2 was suggested to be a potential prognostic and predictive marker. "
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    ABSTRACT: Melanoma is the most malignant type of all skin neoplasms. Its worldwide incidence has steadily increased during the past decades, suggesting a probable melanoma 'epidemic'. Although current clinical, morphologic, and histopathologic methods provide insights into disease behavior and outcome, melanoma is still an unpredictable disease. Once in an advanced stage, it remains a disastrous affliction with scarce therapeutic options. Therefore, significant efforts need to be made in finding informative biomarkers or surrogate markers that could aid or improve early diagnosis of melanoma, its correct staging, the discrimination of other pathological conditions as well as indicate patients' prognosis or the most appropriate therapeutic regimes. Ideally these markers are secreted into body fluids and easily amenable to the design of non-invasive clinical tests. A critical view on the current debate on serologic protein markers, e.g., lactate dehydrogenase, tyrosinase, and melanoma inhibiting activity, and some selected non-protein markers, e.g., 5-S-cysteinyl-dopa and circulating nucleic acids, will be offered and novel innovative approaches currently being explored will be discussed. Special emphasis is put on the S100 family of calcium binding proteins that is more and more emerging as a potentially important group of both molecular key players and biomarkers in the etiology, progression, manifestation, and therapy of neoplastic disorders, including malignant melanoma. Notably, S100B and, possibly, other S100 proteins like S100A4 are assumed to fulfill requirements which make them strong biomarker candidates in melanoma. Moreover, S100 proteins receive attention as possible targets of therapeutic intervention moving closer to clinical impact.
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    • "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. "
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    • "However, NSAIDs may inhibit cancer through various COXindependent pathways as well (Marx, 2001; Elwood et al., 2009). This could be of particular importance in CM, as NSAIDs inhibit the growth of CM cell lines independent of COX-2 (Vogt et al., 2001; Xu, 2002; Chiu et al., 2005; Bundscherer et al., 2008; Lee et al., 2008), and COX-2 is not consistently expressed in CM (Denkert et al., 2001; Vogt et al., 2001; Goulet et al., 2003; Nettelbeck et al., 2003; Kuzbicki et al., 2006; Lee et al., 2008). Thus far, most of the epidemiological studies assessing the chemoprophylactic effects of NSAIDs on CM incidence focus "
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