Estudo dos genes NDRG1, Par-4, osteonectina e pontina, em tecido mamário hiperplásico através de técnica de imunohistoquímica / Study of NDRG1, Par-4, osteonectin and pontin expression in hyperplastic breast lesions with immunohistochemical technique

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

06/05/2011

RESUMO

INTRODUCTION: Breast cancer is a leading cause of death among women all over the Word. Proliferative lesions of the breast are believed to be precursors of or markers of increased risk for breast carcinoma. Although the active research in the field of breast cancer, the early molecular events associated with cancer evolution and progression are still poorly understood. OBJECTIVES: In order to better understand the early events in the breast carcinogenesis, we examined a set of eighty-four proliferative lesions of the breast for the expression of N-myc down regulated gene (NDRG1), Prostate Apoptosis Response-4 (PAR-4), Osteonectin and Pontin, which expression was previously shown by our laboratory to have impact in breast cancer prognosis. METHODS: A tissue microarray were constructed and immunohistochemically tested for Ndrg1, Par-4, Osteonectin and Pontin together with estrogen receptor, low and high weight cytokeratins, aiming to properly characterize the lesions sorted in the tissue microarray. Immunohistochemistry assessment was made quantitative, with the ACIS III Dako quantitative analysis system and TMA application software. RESULTS: After excluding non informative cores, cores with fibroadipose tissue or mammary parenchyma with normal appearing breast epithelium, we ended up with a TMA with 68 breast lesions. Of those, we observed a noticeable positivity of Ndrg1 for lesions with apocrine morphology. Additionally, all cases of florid epithelial hyperplasia showed variable high immunoexpression levels of protein, when compared to the other sorted out lesions in the TMA. Pontin expression level was highest among the breast hyperplasia cases, with statistically significant p value. PAR-4 protein expression was found to be predominantly localized in the nucleous in the non-malignant breast lesions analyzed. Osteonectin exhibited differentiated expression values in the epithelium of hyperplastic breast lesions, papillomas and multiple papillomas when compared to the other types of breast lesions assorted in the TMA. CONCLUSIONS: Our results suggest a possible association of NDRG1 with apocrine differentiation in the breast parenchyma. This observation are consonant with the publish data about the NDRG1 overexpression and the apocrine signature of some mammary cancers. Additionally, we demonstrated that NDRG1 is also overexpressed in some hyperproliferative breast conditions unassociated with apocrine morphology. At present, there is no data available in the in the literature to explain the nuclear translocation of Par-4 in benign breast lesions as observed in our study. However, our findings provide for the first time evidence that PAR-4 is activated in proliferative lesions of the breast indicating that further clinical and experimental studies aiming to investigate PAR-4 function in non neoplastic breast tissue are warranted. Our study also indicated a possible coordinated expression between Osteonectin and NDRG1, at least in apocrine lesions of the breast. Stromal Osteonectin expression seemed to be less intense in breast lesions with papillary architecture, when compared to breast lesions with tendency to recapitulate breast lobular architecture

ASSUNTO(S)

breast disesases breast neoplasm doenças mamárias expressão gênica gene expression n-myc downregulated gene-1 n-myc downstream regulated gene neoplasias de mama osteonectin osteonectina pawr prostate apoptosis response 4 ruvbl1 ruvbl1

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