The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on January 5, 2010). Thesis advisor: William P. Fay. Includes bibliographical references

Orientadores: Maria Salete Costa Gurgel, Sílvia de Barros-Mazon / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-22T03:12:53Z (GMT). No. of bitstreams: 1 Gimenez_RodrigoPinto_D.pdf: 2727620 bytes, checksum: 505f7780aca2f535e4882eb250f83b9d (MD5) Previous issue date: 2013 / Resumo: Introdução: A obesidade tem se mostrado responsável pelo aumento de 30% a 50% dos casos novos de câncer de mama, em particular na pós-menopausa. A mais recente hipótese para explicar tal fato situa os adipócitos e suas funções autócrina, parácrina e endócrina no centro do cenário, através da relação das adipocinas, por ele secretadas, com a obesidade e o câncer de mama. Objetivo: Artigo 1- Comparar o padrão de expressão imunoistoquímica da adiponectina (APN) e dos seus receptores tipos 1 e 2 (adipoR1/R2) no carcinoma invasor (CDI), carcinoma ductal in situ (CDIS) e lesões benignas da mama (BE) e correlacioná-los com parâmetros clínicos e histológicos. Artigo 2- Avaliar a expressão protéica da FABP4 nos tecidos epiteliais e adiposos mamário de portadoras de CDI, CDIS e lesões benignas da mama. Material e Métodos: Foram incluídos os blocos de parafina de 223 mulheres sendo 69 com CDI, 73 com CDIS e 81 com biópsias negativas para câncer de mama, tratadas no CAISM/UNICAMP de janeiro de 2008 a dezembro de 2011, e preparadas lâminas de Tissue Microarray (TMA). A expressão de APN e Adipo R1/R2 foi avaliada no tecido tumoral nos casos CDI e CDIS e no tecido epitelial e nos casos benignos. A expressão de FABP4 foi avaliada no tecido tumoral, na gordura peritumoral (GP) e na gordura mamária distante (GD) nos casos de CDI e CDIS, e no tecido epitelial e gorduras mamários nos casos benignos. Para avaliar uma possível relação entre a expressão dos marcadores entre si e com parâmetros antropométricos, clínicos e histopatológicos, foram utilizados os testes qui-quadrado ou exato de Fisher, Mann-Whitney, Kruskal-Wallis e correlação de Spearman. As determinações foram calculadas considerando o valor de ?=0,05 (p<0,05). Resultados: Artigo 1 - A APN mostrou-se expressa em 65% dos CDI, 48% dos CDIS e 12% das BE e AdipoR1 em 98%, 94% e 71%, respectivamente. Todos os casos de CDI e CDIS expressaram AdipoR2 contra 81% de BE. Nos CDI e CDIS observou-se associação entre maior expressão de APN e tumores RE negativo. No CDIS esta associação foi também observada com RP negativo. Artigo 2 - Observou-se expressão protéica da FABP4 no tecido epitelial em 90% dos CDI, 40% dos CDIS e 28% em BE. Considerando-se a GP e GD esta expressão foi maior nas BE que nos CDI, diferenças consideradas significativas. Nas pacientes com CDI a expressão da FABP4 foi maior quando o diagnóstico ocorreu até 50 anos de idade. A totalidade dos casos expressou moderada a intensamente este marcador no tecido gorduroso periepitelial e distante. Conclusões: As diferenças de expressões protéicas da adiponectina e dos seus receptores AdipoR1/R2 observadas em diferentes diagnósticos mamários sugerem sua participação no complexo mecanismo etiológico destas diferentes condições. Os resultados deste estudo indicam, ainda, que existe uma correlação direta entre expressão protéica da FABP4, câncer de mama e obesidade / Abstract: Introduction: Obesity has been shown to be responsible for a 30 to 50% increase in new breast cancer cases, in particular in the postmenopausal period. The most recent hypothesis that explains this fact places adipocytes and its autocrine, paracrine and endocrine functions at center stage, linking adipokines secreted by adipocytes to obesity and breast cancer. Objective: Article 1- to compare immunohistochemistry expression pattern of adiponectin (APN) and its receptors types 1 and 2 (adipoR1/R2) in invasive carcinoma (IDC), ductal carcinoma in situ (CDIS) and benign breast lesions (BE), correlated with clinical and histological parameters. Article 2- To assess FABP4 protein expression in epithelial and adipose breast tissue in women diagnosed with IDC, DCIS and benign breast lesions. Material and Methods: Paraffin-embedded blocks from 223 women were included. Of the total number of women, 69 had IDC CDI, 73 had CDIS and 81 had biopsies negative for breast cancer. The patients have been treated at CAISM/Unicamp from January 2008 to December 2011 and Tissue Microarray (TMA) slides were constructed. Expression of APN and Adipo R1/R2 was assessed in tumor tissue in cases of IDC and DCIS and in epithelial tissue in benign cases. FABP4 expression was evaluated in tumor tissue, peritumoral fat tissue (PF) and distant fat breast tissue (DF) in cases of IDC and DCIS and in the epithelial tissue and breast fat tissue in benign cases. To assess a possible relationship between marker expression and anthropometric, clinical and histopathological parameters, the chi-square test or Fisher's exact test, Mann-Whitney test, Kruskal-Wallis test and Spearman's correlation were used. Determinations were calculated, considering a value ?=0.05 (p<0.05) as significant. Results: Article 1 - APN was shown to be expressed in 65% of IDC, 48% of DCIS and 12% of BE and AdipoR1 in 98%, 94% and 71%, respectively. All IDC and DCIS cases expressed AdipoR2 versus 81% of BE. In IDC and DCIS, an association between a higher level of APN expression and ER-negative tumors was observed. In DCIS, this association was also observed with PR-negative tumors. Article 2 - FABP4 protein expression was observed in epithelial tissue in 90% of CDI, 40% of DCIS and 28% of BE. Considering PF and DF, FABP4 expression had a higher level in BE than in IDC, a difference that was considered significant. In patients with IDC, FABP4 expression was higher when diagnosis was made in patients aged up to 50 years. In all cases, this marker was moderately to intensely expressed in the peri-epithelial and distant fat tissue. Conclusions: Discrepancies in protein expression of adiponectin and its receptors AdipoR1/R2 observed in different breast diagnoses suggest its participation in the complex etiologic mechanism of these different conditions. Our results indicate that there is a direct correlation between FABP4 protein expression, breast cancer and obesity / Doutorado / Oncologia Ginecológica e Mamária / Doutor em Ciências da Saúde