RESUMO
There is increasing evidence that breast cancers contain tumor-initiating cells with stem cell properties. The importance of estrogen in the development of the mammary gland and in breast cancer is well known, but the influence of estrogen on the stem cell population has not been assessed. We show that estrogen reduces the proportion of stem cells in the normal human mammary gland and in breast cancer cells. The embryonic stem cell genes NANOG, OCT4, and SOX2 are expressed in normal breast stem cells and at higher levels in breast tumor cells and their expression decreases upon differentiation. Overexpression of each stem cell gene reduces estrogen receptor (ER) expression, and increases the number of stem cells and their capacity for invasion, properties associated with tumorigenesis and poor prognosis. These results indicate that estrogen reduces the size of the human breast stem cell pool and may provide an explanation for the better prognosis of ER-positive tumors.
Assuntos
Mama/citologia , Mama/efeitos dos fármacos , Estrogênios/farmacologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Adulto , Antineoplásicos Hormonais/farmacologia , Mama/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Linhagem Celular Tumoral , Feminino , Expressão Gênica/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Glândulas Mamárias Humanas/efeitos dos fármacos , Pessoa de Meia-Idade , Proteína Homeobox Nanog , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Esferoides Celulares/efeitos dos fármacos , Tamoxifeno/farmacologia , Adulto JovemRESUMO
We evaluated the validity and accuracy of cytomorphology and multiparametric flow cytometry (C-FCM) in diagnosing oncohematologic disease in 223 consecutive lymph node biopsy specimens from patients with lymphadenopathy, from 2004 to 2007. C-FCM and histopathologic studies were interpreted independently by hematologists and pathologists, respectively. C-FCM detected neoplastic disorders in 133 samples (59.6%): 92 non-Hodgkin lymphomas (NHLs; 41.3%), 21 Hodgkin lymphomas (HLs; 9.4%), 19 malignant nonhematologic neoplasms (8.5%), and 1 multiple myeloma (0.4%). Sensitivity and specificity were 87.25% and 95.95%, respectively. Positive predictive value and negative predictive value (NPV) were 97.74% and 78.89%, respectively. Sensitivity and NPV were 94.79% and 96.81% upon excluding HL and malignant nonhematologic neoplasms from the analysis. Of the 92 NHLs, 89 (97%) were categorized according to the 2001 World Health Organization classification of hematolymphoid neoplasms with a concordance of 87%. The C-FCM study was significantly faster than the histopathologic study. C-FCM has high sensitivity and specificity, allowing for a valid and reliable diagnosis, especially in NHLs and enabling their subclassification. C-FCM is faster than the histopathologic examination, allowing for therapeutic decisions to be made quickly. However, in the samples in which C-FCM cannot establish a diagnosis, histopathologic results are needed.