The value of cyclooxygenase-2 expression in differentiating between early melanomas and histopathologically difficult types of benign human skin lesions

Abstract

Early cutaneous melanomas may present a substantial diagnostic challenge. We have already reported that expression of cyclooxygenase-2 (COX-2) may be useful for differentiating between cutaneous melanomas and naevi. The purpose of this study was to examine the value of COX-2 in a challenging task of differential diagnosis of early melanomas and melanocytic naevi considered by histopathologists as morphologically difficult to unequivocally diagnose as benign lesions. The material for the study comprised formalin-fixed paraffin-embedded samples of 46 naevi (including 27 cases of dysplastic, Spitz and Reed naevi) and 30 early human cutaneous melanomas. The expression of COX-2 was detected immunohistochemically. Melanomas expressed COX-2 significantly more strongly compared with naevi. The test, on the basis of determination of the percentage fractions of COX-2-positive cells, allows for differentiation of early skin melanomas and naevi with high sensitivity and specificity. Receiver operating characteristic analysis of the test results yielded areas under receiver operating characteristics curves (AUC)=0.946±0.030 for central regions and AUC=0.941±0.031 for the peripheries of the lesions. The performance of the test in differentiating between melanomas and the naevi group comprising dysplastic, Spitz and Reed naevi was also good, with AUC=0.933±0.034 and 0.923±0.037 for the central and the border regions of the lesions, respectively. Using a more complex diagnostic algorithm also accounting for the staining intensity did not result in an improvement in the resolving power of the assay. A diagnostic algorithm using differences in the percentage fractions of cells expressing COX-2 may serve as a useful tool in aiding the differential diagnosis of 'histopathologically difficult' benign melanocytic skin lesions and early melanomas.

Investigating associations of cyclooxygenase-2 expression with angiogenesis, proliferation, macrophage and T-lymphocyte infiltration in canine melanocytic tumours

“…When all tumour samples were considered, including malignant and benign melanocytic tumours, COX-2 immunoexpression presented associations with proliferation, angiogenesis and immune infiltration biomarkers. This heterogeneous group of tumours might have skewed the analysis as melanocytomas tend to have lower COX-2 expression [14,15] and naturally reduced proliferation and angiogenesis compared with the malignant melanomas, as confirmed in our results.…”

“…Also, the fact that COX-2 expression was found to be absent in cutaneous melanocytomas, but present in malignant cutaneous melanomas, suggests that COX-2 may be associated with the acquisition of malignancy during the tumorigenesis of melanocytic neoplasms [14]. Similarly, in human cutaneous melanomas, COX-2 expression has been proposed as a new biomarker to help pathologists distinguish benign melanocytic lesions from early malignant melanomas [15].…”

Immunohistochemical expression of cyclooxygenase‐2 (COX‐2) in oral nevi and melanoma

“…Indeed, cutaneous melanomas and compound melanocytic nevi showed similar results, as also observed by Denkert et al and Bianchini et al . Kuzbicki et al demonstrated that the immunohistochemical intensity of COX‐2 is associated with Clark level and Breslow thickness, suggesting this protein as a molecular prognostic marker. We also found a single case of cutaneous melanoma with Clark level III and Breslow thickness >2 mm exhibiting high COX‐2 positivity, but this finding was different from those found in oral melanomas, in which both invasive and in situ lesions showed high positivity for COX‐2.…”

“…Currently, there is little evidence to claim that oral melanocytic nevi increases the risk for oral melanomas, but the development of melanomas has been attributed of being preceded by pigmented lesions of unknown characteristics . Kuzbicki et al showed COX‐2 positive cells only occasionally in benign melanocytic lesions, particularly in dysplastic nevi. It would be interesting to determine COX‐2 expression in atypical melanocytic hyperplasias of the oral cavity, but considering their rarity, multicentric studies are encouraged for this purpose.…”

Aspirin and Other NSAIDs as Chemoprevention Agents in Melanoma

“…COX-2 may be a reasonable target in melanoma, as it is generally not expressed in benign melanocytic nevi but is highly expressed in most melanomas (41, 42). Analysis of primary and metastatic melanoma lesions revealed increased COX-2 expression with melanoma progression (43), and that high COX-2 expression correlates inversely with patient survival (44).…”