Prognostic significance of cyclooxygenase 2 and phosphorylated Akt1 overexpression in primary nonmetastatic and metastatic cutaneous melanomas

Autor(es)

Soares, Ciro D. ; Borges, Camilla F. ; Sena-Filho, Marcondes ; de Almeida, Oslei P. ; Stelini, Rafael F. ; Cintra, Maria L. ; Graner, Edgard ; Zecchin, Karina G. ; Jorge, Jacks

• Tipo de documento: Artigo Científico
• Fonte: Melanoma Research; v. 27, n. 5, p. 448-456, OCT 2017.
• Citações Web of Science: 9

Resumo

Cyclooxygenase 2 (COX-2) and phosphorylated Akt1 (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 by correlating with the cellular proliferation index (as revealed by minichromosome maintenance 2 expression) and the outcome of patients with malignant melanomas. Seventy-seven biopsies of malignant melanomas, including 42 primary nonmetastatic melanomas (PNMMs), 12 primary metastatic melanomas (PMMs), and 23 metastatic melanomas (MMs), were retrospectively selected. Tissue microarrays were developed and submitted for immunohistochemical staining for COX-2, p-Akt1, and minichromosome maintenance 2. Increased COX-2 cytoplasmic staining patterns were observed in PMM and MM when compared with 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). Coexpression 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. However, further studies are required to elucidate the biological role of these biomarkers during the progression of MM events. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved. (AU)

• Processo FAPESP: 13/25305-9 - Correlação dos fatores de transcrição RUNX1 e ETV5 com a expressão e atividade das metaloproteinases 2 e 9 em lesões potencialmente malignas e carcinomas espinocelulares bucais
• Beneficiário: Jacks Jorge Junior
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/25905-1 - Expressão de Akt, COX-2, RUNX1 e metaloproteinases em melanomas metastáticos e Prospecção biotecnológica de moléculas com atividade antitumoral
• Beneficiário: Ciro Dantas Soares
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/14008-0 - Correlação entre prognóstico de melanoma maligno humano e expressão da enzima ácido graxo sintase e de proteínas envolvidas no ciclo celular e na angiogênese
• Beneficiário: Camilla Borges Ferreira Gomes
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/13834-4 - Correlação entre prognóstico de melanoma maligno humano e expressão da enzima ácido graxo sintase e de proteínas envolvidas no ciclo celular e na angiogênese
• Beneficiário: Karina Gottardello Zecchin
• Modalidade de apoio: Auxílio à Pesquisa - Regular