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Prognostic significance of cyclooxygenase 2 (COX-2) and p-Akt1 overexpression in primary non-metastatic and metastatic cutaneous Melanomas


Cyclooxygenase 2 (COX-2) and p-Akt1 are associated with tumor spreading, cell proliferation, high metabolism, and angiogenesis in solid tumors. This study aimed to investigate COX-2 and p-Akt1 expression in primary and metastatic melanomas, through correlation with the cellular proliferation index (as revealed by minichromosome maintenance 2 [Mcm-2] expression) and the outcome of patients with malignant melanomas. Seventy-seven biopsies of malignant melanomas, including 42 primary non-metastatic melanomas (PNMM), 12 primary metastatic melanomas (PMM), and 23 metastatic melanomas (MM), were retrospectively selected. Tissue microarrays were developed and submitted to immunohistochemical staining for COX- 2, p-Akt1, and Mcm-2. Increased COX-2 cytoplasmic staining patterns were observed in PMM and MM when compared to PNMM (P = 0.0011). Higher nuclear and cytoplasmic expression of p-Akt1 was more closely associated with PMM than with MM and PNMM (p < 0.00001). Co-expression of these biomarkers was closely correlated with lower overall survival rates in melanomas. Furthermore, we observed a statistically significant positive correlation between the mitosis index and increased COX-2 expression (P = 0.0135), and between p-Akt1 (P = 0.0038) and the cellular proliferation index (P = 0.0060). Taken together, our findings demonstrate that COX-2 and p-Akt1 play an important combined role during melanoma progression and are associated with highly metastatic tumors and survival rates in patients with MM. In addition, these biomarkers can be used to predict melanoma prognosis independently of metastatic status. Further studies are however required to elucidate the biological role of these biomarkers during the progression of melanoma metastatic events. (AU)

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