Análisis de las variables clínicas, anatomopatológicas y moleculares asociadas al carcinoma ductal infiltrante esporádico de mama

Abstract

TITULO: ANÁLISIS DE LAS VARIABLES CLÍNICAS, ANÁTOMO PATO LOGI CAS Y MOLECULARES ASOCIADAS AL CARCINOMA DUCTAL INFILTRANTE ESPORÁDICO DE MAMA RESUMEN: Breast cancer is a heterogeneous type of cancer with different prognosis, and molecular studies are necessary to evaluate parameters that can hetp clinicians to characterize more aggressive breast tumours. The aggressiveness depends on the expression of proteins involved in cell adhesion, cell cycle and signal transduction. The hypermethylation of promoter of tumors suppressor genes, the presence of mutations, and loss of heterozygosity contribute to the alteration of gene expression and cancer progression. The Ph thesis deals with the study of the hypermethylation of TSGs, p53 mutations and LOH of 16q22.1, the expression of proteins by immunohistochemistry, the expression of E-cadherin and caspase 3 in primary cultures, the cell migration properties, the clinicopathological features in patients with invasive breast ductal carcinoma from the Hospital of Navarra and the distribution of these parameters in the different subtypes (luminal, Her2, basal and normal). METHODS: Primary cultures from tumors ¡Y2 cm. were prepared and dna from frozen tumour was obtained; the techniques used were MS-PCR, PCR-SSCP, invasión assays, Western blot and immunohistochemistry in tissue microarrays. RESULTS: cell viability and migration was associated to histology grade and E-cadherin expression, respectively, and bel-2 expression was a good prognosis factor. CDH-1 hypermethylation was present in Her2 tumors, bel-2 and cyclin Di proteins were expressed in luminal tumors and beta-catenin in basal tumors. We confirmed the better prognosis for luminal tumors. In conclusión, the hypermethylation and the expression of certain proteins differ between breast cancer subtypes, and could be used as markers that help to identify these subtypes