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

Author(s)

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

• Document type: Journal article
• Source: Melanoma Research; v. 27, n. 5, p. 448-456, OCT 2017.
• Web of Science Citations: 9

Abstract

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)

• FAPESP's process: 13/25305-9 - Correlation of the transcription factors RUNX1 and ETV5 with the expression and activity of metalloproteinases 2 and 9 in oral potentially malignant lesions and squamous cell carcinomas
• Grantee: Jacks Jorge Junior
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/25905-1 - Akt, COX-2, RUNX1 and MMPs expression in metastatic melanomas and Biotechnology prospection of molecules with antineoplastic activity
• Grantee: Ciro Dantas Soares
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/14008-0 - Correlation between fatty acid synthase, and proteins involved in cell cycle and angiogenesis with human malignant melanoma prognosis
• Grantee: Camilla Borges Ferreira Gomes
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/13834-4 - Correlation between fatty acid synthase, and proteins involved in cell cycle and angiogenesis with human malignant melanoma prognosis
• Grantee: Karina Gottardello Zecchin
• Support Opportunities: Regular Research Grants