Melanomas of sun protected sites: immunohistochemical and pirosequencing study of MITF and c-kit cascades

Abstract

The melanocytes are precursor cells of melanocytes that originate in the neural crest of vertebrates. These cells migrate through the lateral way to: skin, and oro and nasal mucosa, and other places, where they are responsible for the color of skin, hair and eyes. On skin it has a protective function against the effects of sun radiation, but its role in the oral mucosa is still uncertain.The mutations involved in the oncogenic transformation of these cells, which originate from various types of melanoma, have been recognized through signaling pathways responsible for the survival and proliferation of melanocyte lineage. Changes in the MAPK pathway are commonly observed in melanomas as well as in KIT and MITF, they are able to transform melanocytes and contribute to the metastatic potential of melanoma.In cutaneous melanomas of sun-exposed areas, the MAPK pathway is a signaling cascade that has a main role in the phosphorylation and activation of MITF after stimulation of SCF ligand to the receptor tyrosine kinase KIT. In a previous study, during the PhD program, it was demonstrated the importance of mutations in components of the MAPK pathway in primary melanomas of the oral mucosa (sun protected site) (see appendix). This work led to publication and awards at international congresses. Today, scientific advances over the MAPK pathway have been applied to the development of new chemotherapeutic methods, a clear example of research that goes from the bench to the bedside of patients.Now, in this new phase of the study of the molecular pathways of melanomas sun protected sites, it is imperative to advance the knowledge of complementary pathways to MAPK. Thus, we propose to analyze patterns of protein expression and mutation of KIT and MITF in melanomas of the oral mucosa and acral, and correlate the data obtained in experiments with the clinical-evolutionary cases analyzed.It is expected that the results of this study can corroborate previous study of MAPK and studies in the literature relating to sun protected sites melanomas and contribute to the diagnosis and treatment of this subgroup of melanoma. (AU)