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Gomes D.S.,Federal University of Minas Gerais | Porto S.S.,Federal University of Minas Gerais | Rocha R.M.,Laboratory of Investigative Pathology | Gobbi H.,Federal University of Minas Gerais
Diagnostic Pathology | Year: 2013

Background: The distinction between lobular neoplasia of the breast and ductal carcinoma in situ has importanttherapeutic implications. In some cases, it is very difficult to determine whether the morphology of the lesion isductal or lobular. The aim of this study was to evaluate the value of E-cadherin and β-catenin expression throughthe immunophenotypical characterization of carcinoma in situ with mixed pattern (CISM).Methods: A total of 25 cases of CISM were analyzed considering cytology/mixed architecture (ductal and lobular),nuclear pleomorphism, loss of cell cohesion, and presence of comedonecrosis. The immunophenotype pattern wasconsidered E-cadherin positive and β-catenin positive, or negative.Results: Nineteen (76%) cases presented a mixed cytology and / or architectural pattern, two (8%) presented nuclearpleomorphism, two (8%) presented mixed cytology and nuclear pleomorphism, and two (8%) presentedcomedonecrosis and nuclear pleomorphism. A complete positivity for E-cadherin and β-catenin was observed in 11 cases (44%). In one case, the lesion was negative for both markers and showed nuclear pleomorphis. Thirteen lesionsshowed negative staining in areas of lobular cytology and positive staining in cells presenting the ductal pattern.Conclusions: The expression of E-cadherin and β-catenin, combined with cytological and architectural analysis, mayhighlight different immunophenotypes and improve classification of CISM. © 2013 Gomes et al.; licensee BioMed Central Ltd.

Renno A.L.,University of Campinas | Alves-Junior M.J.,University of Campinas | Rocha R.M.,Laboratory of Investigative Pathology | De Souza P.C.,University of Campinas | And 11 more authors.
Toxicologic Pathology | Year: 2015

Simvastatin, a competitive inhibitor of HMG-CoA reductase widely used in the treatment and prevention of hyperlipidemia-related diseases, has recently been associated to in vitro anticancer stem cell (CSC) actions. However, these effects have not been confirmed in vivo. To assess in vivo anti-CSC effects of simvastatin, female Sprague-Dawley rats with 7,12-dimethyl-benz(a)anthracene (DMBA)-induced mammary cancer and control animals were treated for 14 days with either simvastatin (20 or 40 mg/kg/day) or soybean oil (N = 60). Tumors and normal breast tissues were removed for pathologic examination and immunodetection of CSC markers. At 40 mg/kg/day, simvastatin significantly reduced tumor growth and the expression of most CSC markers. The reduction in tumor growth (80%) could not be explained solely by the decrease in CSCs, since the latter accounted for less than 10% of the neoplasia (differentiated cancer cells were also affected). Stem cells in normal, nonneoplastic breast tissues were not affected by simvastatin. Simvastatin was also associated with a significant decrease in proliferative activity but no increase in cell death. In conclusion, this is the first study to confirm simvastatin anti-CSC actions in vivo, further demonstrating that this effect is specific for neoplastic cells, but not restricted to CSCs, and most likely due to inhibition of cell proliferation. Copyright © 2014 by The Author(s).

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