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Doctoral Thesis
DOI
10.11606/T.59.2011.tde-04042012-144223
Document
Author
Full name
Marina Piacenti da Silva
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2011
Supervisor
Committee
Poletti, Martin Eduardo (President)
Barroso, Regina Cely Rodrigues
Moreira, Silvana
Perez, Carlos Alberto
Silva, Alfredo Ribeiro da
Title in Portuguese
Papel dos elementos-traço em neoplasias mamárias: estudo através de técnicas espectroscópicas de fluorescência de raios X e análises imunohistoquímicas
Keywords in Portuguese
Câncer de mama
Elementos-traço
Fluorescência de Raios X
Imunohistoquímica.
Marcadores tumorais
Abstract in Portuguese
Neste trabalho foi avaliado o papel de elementos-traço em tecidos mamários neoplásicos e seu potencial como marcadores tumorais e fatores prognósticos. As concentrações dos elementos cálcio, ferro, cobre e zinco em tecidos normais e neoplásicos foram determinadas através de técnicas de fluorescência de raios X por dispersão por energia e por reflexão total. Modelos diagnósticos (análise de discriminante e curvas ROC - Receiver Operating Characteristic) baseados na análise estatística das distribuições de concentrações dos elementos mostraram que é possível classificar os diversos tipos de tecidos mamários (normais, benignos e malignos). Foi possível ainda avaliar a expressão dos elementos-traço e correlacioná-la com dados clinicopatológicos de importância prognóstica e com a sobrevida global de pacientes com câncer de mama. Os resultados mostraram que a expressão dos elementos-traço pode ser utilizada como marcador tumoral e fator prognóstico. Através da técnica de micro fluorescência de raios X, as distribuições espaciais dos elementos-traço foram avaliadas e comparadas com a expressão imunohistoquímica de metaloproteinases de matriz (MMPs), seus inibidores (TIMPs) e com o fator de crescimento vascular endotelial (VEGF). Os resultados mostraram que os elementos Fe, Cu e a expressão do VEGF estão correlacionados, sugerindo que o acúmulo destes elementos pode estar associado ao processo angiogênico em neoplasias mamárias. Foram observadas ainda correlações entre as distribuições de Ca, Zn e a expressão de MMPs e TIMPs, possivelmente devido à presença destes metais nestas proteínas.
Title in English
Role of trace elements in breast cancer: Study by X-Ray Fluorescence spectroscopy techniques and Immunohistochemical analysis.
Keywords in English
Breast Cancer
Immunohistochemistry.
Trace elements
Tumoral biomarkers
X-Ray Fluorescence
Abstract in English
In this work the role of trace elements in neoplastic breast tissues were evaluated to be applied as tumoral biomarkers and prognostic factors. Concentrations of trace elements like calcium, iron, copper, and zinc in normal and neoplastic tissues have been determinate by X-Ray Fluorescence (XRF) spectroscopic techniques. Diagnostic models (discriminant analysis and ROC curves) based on statistics analysis of trace elements concentrations distributions reveal that it is possible to classify different breast tissues (normal, benign and malignant). Also, it was possible to evaluate trace elements expression and correlate them with clinic-pathological data that are important in prognostic and the overall survival of breast cancer patients. The results presented have shown that trace elements expression can be used as tumoral biomarkers and prognostic factors. The spatial distributions of trace elements were evaluated by micro-XRF and the results were compared to immunohistochemical expression of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), as well as with vascular endothelial growth factor (VEGF). The results reveal that elements Fe, Cu and VEGF expression are correlated, indicating that the higher levels of these elements are associated with angiogenic process in breast cancer. Also, correlations between Ca, Zn and MMPs and TIMPs expression have been observed, possibly due those metals are present in these proteins.
 
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Marinacorrigida.pdf (3.78 Mbytes)
Publishing Date
2012-05-09
 
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