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| Author(s): |
Beatriz Areias Sangiuliano
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) |
| Defense date: | 2016-02-05 |
| Examining board members: |
Jose Ernesto Belizario;
Durvanei Augusto Maria
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| Advisor: | Jose Ernesto Belizario |
| Abstract | |
Cutaneous melanoma is the skin neoplasia with the highest mortality rate and great unpredictability in its evolution. In disseminated disease, the treatment options are little effective. The research for new tumor markers allows a better understanding of the pathogenesis of melanoma and enables the discovery of molecular targets. The Dermcidin protein (DCD) was identified among the nine genes of a gene signature predicting clinical diagnosis of human melanoma, although many authors differ on its role in the disease and the molecular mechanisms by which DCD acts in tumors remain unclear. The present study aimed to investigate the role of DCD in the tumorigenesis of malignant melanoma and to correlate its expression with clinical, demographic and pathologic data of patients. Using the technique of immunohistochemistry in TMA slides (tissue microarray), the expression pattern of DCD was analyzed in tumoral tissue of two cohorts of patients, the first with 53 cases treated in hospital AC Camargo, predominantly caucasians, and the second with 48 cases, all Asians, commercially obtained from IMGENEX company. The in situ analysis of Dermcidin showed that the protein is expressed in a heterogeneous manner in tumor cells, and can occur in non-melanocytic as well as in melanocytic tumors. In the primary melanoma, DCD expression was more seen in tumors located in the regions of torso and upper limbs. In the metastases, the protein was found predominantly in cells in transit in the lymph nodes (69.23% of cases). Analyzing the 101 patients of the two cohorts together, by the Kaplan-Meier method, it was confirmed that patients with DCD-negative, the survival rate was 65.54% in 60 months, and 62.86% in 130 months, while the group of patients with DCD-positive tumor had 43.33% in 5 years, and 22.12% in 130 months, knowing that a difference between the groups was significative (p=0.0229). The death rate of patients with DCD-positive tumor was higher, 56%, when compared with the death rate of individuals with DCD-negative tumor, 33.33% (p=0.0281). It was also found a trend of tumors expressing DCD related to patients older than 50 years (p=0.1057). In a search of 4 different studies grouping the DNA sequencing tumor of 515 patients we observed that the DCD gene, in melanoma, is not predominantly amplified, but mutated. The E43K substitution was the most frequent alteration, corresponding to 70% of cases of gene mutation. When comparing the available cases of mutations in DCD with the genes BRAF, NRAS, MITF, CDKN2A, ERBB4, we found an association with the BRAF V600E mutation in cases where occurred the DCD E43K. By having high frequency in melanomas (ranging between 45 and 54%) and being an indicator of poor prognosis for the neoplasia, DCD expression can be considered as a potential biomarker (AU) | |
| FAPESP's process: | 13/14423-0 - ANALYSIS OF DERMCIDIN'S EXPRESSION IN HUMAN MALIGNANT MELANOMA AND IT'S ASSOCIATION WITH GENE AMPLIFICATION IN CHROMOSOME 12 |
| Grantee: | Beatriz Areias Sangiuliano |
| Support Opportunities: | Scholarships in Brazil - Master |