Phosphorylated Akt1 expression is associated with poor prognosis in cutaneous, oral and sinonasal melanomas.

Ciro Soares,Fernanda Viviane Mariano,Maria Goretti Freire De Carvalho,Rodrigo Ribas Dias Dos Reis,Albina Altemani,Thayná Melo De Lima Morais,Roman Carlos,Luciana Schultz Amorim,Marcelo Brum Corrêa,Oslei Paes De Almeida,Jacks Jorge

doi:10.18632/oncotarget.26458

Ciro Soares, Fernanda Viviane Mariano + Show 9 more

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https://doi.org/10.18632/oncotarget.26458

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Abstract

Melanomas are highly aggressive tumours derived from melanocytes, which occur most commonly in the skin. Occasionally, these tumours may appear in oral and sinonasal mucous membranes. In this study, we performed a comparative analysis of the Phosphorylated Akt1 (p-Akt1) expression in 144 patients affected by cutaneous (CM), 34 oral cavity (OM), and 31 sinonasal melanomas (SNM). Similar to the metastatic cutaneous melanomas, p-Akt1 was overexpressed in 17/34 of the oral cavity and 20/31 of the sinonasal melanomas. In addition, the p-Akt1-nuclear expression was associated with poorer cancer-specific survival in cutaneous (P < .0001), oral (P < .0001), and sinonasal (P = .001) melanomas. Multivariate analysis showed p-Akt1 to be an independent prognostic marker in oral (P = .041) and sinonasal (P < .0001) melanomas patients. In conclusion, p-Akt1 overexpression is an independent prognostic marker in mucosal melanomas and is significantly up-regulated in sinonasal melanomas. As both mucosal and metastatic cutaneous melanomas showed high frequency of p-Akt1 expression, these findings suggest that mucosal melanomas have a biological behaviour, similar to the aggressive cutaneous melanomas.

Highlights

Cutaneous melanomas represent about 1.6% of all cancers, and discreet advances in their treatment have been made over the last decades
We performed a comparative analysis of the Phosphorylated Akt1 (p-Akt1) expression in 144 patients affected by cutaneous (CM), 34 oral cavity (OM), and 31 sinonasal melanomas (SNM)
P-Akt1 overexpression is an independent prognostic marker in mucosal melanomas and is significantly up-regulated in sinonasal melanomas. As both mucosal and metastatic cutaneous melanomas showed high frequency of p-Akt1 expression, these findings suggest that mucosal melanomas have a biological behaviour, similar to the aggressive cutaneous melanomas

Summary

Introduction

Cutaneous melanomas represent about 1.6% of all cancers, and discreet advances in their treatment have been made over the last decades. This tumour still remains deathly, especially the metastatic disease [1]. Controlling the advanced-stage disease is the major problem for the treatment of melanomas. The etiologic factors and the clinical and biological behaviour of cutaneous melanomas are very distinct from the other melanomas [7, 8]. Clinicopathological parameters determine the prognosis and staging of the melanomas from different anatomic sites [10]

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