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Morphological, molecular and microenvironment factors associated to stromal invasion risk in breast ductal carcinomas in situ

Grant number: 11/22993-6
Support type:Regular Research Grants
Duration: April 01, 2012 - March 31, 2014
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Filomena Marino Carvalho
Grantee:Filomena Marino Carvalho
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Ductal carcinomas in situ (DCIS) are heterogeneous breast lesions regarding morphology and risk of evolution. The estimation of the biological behavior through the histological characteristics has several limitations, starting with the subjectivity inherent in the method. The research of molecular profiles in DCIS using the same criteria applied to the invasive carcinomas shows differences between in situ and invasive components. These studies point to possible influence of other factors in the neoplastic progression. Along the same lines, several studies on carcinogenesis demonstrate that the major genetic differences occur between the normal tissue and the precursor lesion, but the passage to invasive form may depend on other factors. Myoepithelial cells (MEC) correspond to active component of microenvironment and are likely to be involved in invasiveness. In this retrospective study we constructed tissue microarrays blocks with samples of DCIS, characterized according patient's age, molecular subtype, grade and presence of invasion. The molecular types of in situ and invasive components will be based on immunohistochemical expression of ER, PR, HER2, EGFR and CK 5/6, plus KI-67for invasive carcinomas. MEC will be evaluated by different immunohistochemical markers (CK5/6, Smooth Muscle Actin, CD10, p63, calponin, SMMHC) and analyzed within the different subgroups of DCIS to determine modifications related to greater likelihood of invasion. Changes in molecular profile between in situ and invasive components will be explored according the influence of molecular profile, grade and pattern of MEC profile. The myoepithelial phenotype definition can allow this information to be added to the characterization of the DCIS for better prediction of the risk of invasion and appropriate therapeutic planning. (AU)