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Evidence that molecular changes in cells occur before morphological alterations during the progression of breast ductal carcinoma

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Autor(es):
Castro, Nadia P. ; Osorio, Cynthia A. B. T. ; Torres, Cesar ; Bastos, Elen P. ; Mourao-Neto, Mario ; Soares, Fernando A. ; Brentani, Helena P. ; Carraro, Dirce M.
Número total de Autores: 8
Tipo de documento: Artigo Científico
Fonte: BREAST CANCER RESEARCH; v. 10, n. 5, p. 14-pg., 2008-01-01.
Resumo

Introduction Ductal carcinoma in situ (DCIS) of the breast includes a heterogeneous group of preinvasive tumors with uncertain evolution. Definition of the molecular factors necessary for progression to invasive disease is crucial to determining which lesions are likely to become invasive. To obtain insight into the molecular basis of DCIS, we compared the gene expression pattern of cells from the following samples: non-neoplastic, pure DCIS, in situ component of lesions with co-existing invasive ductal carcinoma, and invasive ductal carcinoma. Methods Forty-one samples were evaluated: four nonneoplastic, five pure DCIS, 22 in situ component of lesions with co-existing invasive ductal carcinoma, and 10 invasive ductal carcinoma. Pure cell populations were isolated using laser microdissection. Total RNA was purified, DNase treated, and amplified using the T7-based method. Microarray analysis was conducted using a customized cDNA platform. The concept of molecular divergence was applied to classify the sample groups using analysis of variance followed by Tukey's test. Results Among the tumor sample groups, cells from pure DCIS exhibited the most divergent molecular profile, consequently identifying cells from in situ component of lesions with coexisting invasive ductal carcinoma as very similar to cells from invasive lesions. Additionally, we identified 147 genes that were differentially expressed between pure DCIS and in situ component of lesions with co-existing invasive ductal carcinoma, which can discriminate samples representative of in situ component of lesions with co-existing invasive ductal carcinoma from 60% of pure DCIS samples. A gene subset was evaluated using quantitative RT-PCR, which confirmed differential expression for 62.5% and 60.0% of them using initial and partial independent sample groups, respectively. Among these genes, LOX and SULF-1 exhibited features that identify them as potential participants in the malignant process of DCIS. Conclusions We identified new genes that are potentially involved in the malignant transformation of DCIS, and our findings strongly suggest that cells from the in situ component of lesions with co-existing invasive ductal carcinoma exhibit molecular alterations that enable them to invade the surrounding tissue before morphological changes in the lesion become apparent. (AU)

Processo FAPESP: 06/02670-0 - Análise do perfil de expressão gênica de carcinoma ductal in situ e invasivo em tumores de mama através da técnica de microarray
Beneficiário:Nádia Pereira de Castro
Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 98/14335-2 - Antonio Prudente Cancer Research Center
Beneficiário:Fernando Augusto Soares
Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs