RESUMO
Two main models to account for the heterogeneous expression of estrogen receptors (ER) and progesterone receptors (PR) in human breast cancer have been proposed: the clonal model and the stem cell model. The authors previously provided evidence supporting the stem cell model since it was found that most of the proliferating cells in ER-positive (ER+) human breast cancer lack ER and that the ER-negative (ER-) and ER+ subpopulations are interrelated. The authors have analyzed in eighteen ER+/PR+ primary breast tumors the simultaneous expression of ER or PR (by immunohistochemistry) and DNA synthesis (by autoradiography) after 30 minutes of 3H-thymidine incorporation. The authors demonstrated that: (1) the average numbers of ER+ and PR+ cells were similar (36.8 +/- 10.7% and 39.3 +/- 17.6%, respectively); (2) The thymidine-labeling indexes of the ER+, ER-, PR+, and PR- subpopulations were 0.53 +/- 0.69%, 0.74 +/- 0.49%, 0.21 +/- 0.21 and 0.94 +/- 0.54%, respectively; and (3) 75.2% of the DNA-synthesizing cells were ER-, and 88.8% of them were PR-. The authors conclude that the cellular subpopulations expressing ER and PR were not identical, and the expression of PR was associated with a lower rate of cellular proliferation than was ER expression.
Assuntos
Neoplasias da Mama/química , DNA de Neoplasias/análise , Receptores de Progesterona/análise , Neoplasias da Mama/genética , Carcinoma/química , Carcinoma/genética , Replicação do DNA/fisiologia , Feminino , Humanos , Imuno-Histoquímica , Receptores de Estrogênio/análise , Reprodutibilidade dos TestesRESUMO
The primary breast tumors of 27 patients were analyzed for the expression of estrogen receptors (ER) and DNA synthesis. Seventeen tumors were ER-positive, and the simultaneous expression of ER and DNA synthesis could be analyzed in 14 ER-positive tumors. DNA synthesis was measured through the thymidine labeling index (TLI). ER expression was detected by immunohistochemistry with monoclonal antibodies. In these tumors, 38.6% +/- 13.1% of the cells were ER-positive (average TLI = 0.60% +/- 0.70%), as opposed to the presence of 61.4% +/- 13.1% of ER-negative cells (average TLI = 0.65% +/- 0.53%). In 12 of 14 tumors, both ER-positive and ER-negative cells were found to be engaged in DNA synthesis, whereas in two tumors only ER-negative cells were synthesizing DNA. On the basis of the TLI and the proportion of ER-negative and ER-positive cells in the total population, it is suggested that the ER-positive and ER-negative compartments are interrelated in most tumors. In five tumors, the ER-negative compartment would be a precursor of the ER-positive segment, whereas in six tumors the ER-positive segment appears to be a precursor of the ER-negative one. In three tumors, no evidence of an interrelationship between both segments could be found. In the 14 tumors analyzed, it also was found that 69.1% +/- 21.3% of the DNA-synthesizing cells were ER-negative; this probably accounts for the temporary remissions observed after hormonal treatment in breast cancer.
Assuntos
Neoplasias da Mama/metabolismo , DNA/biossíntese , Receptores de Estrogênio/análise , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Humanos , Imuno-Histoquímica , Índice Mitótico , Proteínas de Neoplasias/análise , Estadiamento de NeoplasiasRESUMO
In human breast cancer the proliferating cells appear to differ from those containing estrogen receptors (ER) as shown by studies on isolated cellular subpopulations. In this paper the in vitro effect of 17-beta-estradiol on cell proliferation in 30 primary breast tumors was studied. The effect of several estradiol concentrations was assayed, and the influence of diethylstilbestrol, tamoxifen, and nafoxidine was also tested. The response to these compounds was measured through the thymidine labeling index (TLI). When exposed to 10(-9) mol/l and 10(-8) mol/l estradiol, 14 of 19 ER-positive tumors and six of 11 ER-negative tumors were induced to further proliferate. The TLI increase over the control was 219% (P less than 0.05) at 10(-9) mol/l E2 and 258% (P less than 0.05) at 10(-8) mol/l E2 for ER-positive tumors, and 233% (0.1 less than P less than 0.2) at 10(-9) mol/l E2 and 321% (0.1 less than P less than 0.2) at 10(-8) mol/l E2 for ER-negative tumors. The addition of diethylstilbestrol and antiestrogens in vitro inhibited, to varying degrees, the estradiol-induced increase in the TLI irrespective of the ER-status. The response to E2 was correlated with the expression of the ras p21 protein and carcinoembryonic antigen. It was found that the ras p21 protein is preferentially expressed in ER-negative tumors, the opposite being true for carcinoembryonic antigen. The ras p21 protein is preferentially expressed in those ER-positive tumors that do not respond to estradiol with an increase in the TLI.
Assuntos
Neoplasias da Mama/patologia , Estradiol/farmacologia , Neoplasias da Mama/análise , Antígeno Carcinoembrionário/análise , Divisão Celular/efeitos dos fármacos , Replicação do DNA/efeitos dos fármacos , DNA de Neoplasias/análise , Dietilestilbestrol/farmacologia , Humanos , Nafoxidina/farmacologia , Proteínas de Neoplasias/análise , Neoplasias Hormônio-Dependentes/análise , Neoplasias Hormônio-Dependentes/patologia , Proteínas Proto-Oncogênicas/análise , Proteínas Proto-Oncogênicas p21(ras) , Receptores de Estrogênio/análise , Estimulação Química , Tamoxifeno/farmacologia , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
El presente trabajo actualiza el conocimiento del leiomioblastoma, raro tumor de estirpe muscular lisa que puede observarse en casi todos los organos del tubo digestivo. Su evolucion es lenta y su sintomatologia imprecisa, a veces seudoulcerosa y otras como hemorragia digestiva. Su histologia es muy caracteristica con celulas poliedricas provistas de un halo perinuclear que permite su identificacion precisa. En alrededor del 14% de los casos descriptos presenta evolucion maligna con invasion de organos contiguos con metastasis ganglionares, peritoneales o hepaticas. En sus formas malignas tiene muy lenta evolucion por lo cual el criterio terapeutico, aun con invasion por contiguidad, admite una actitud resectiva amplia con satisfactoria sobrevida. En este trabajo se presenta un caso de evolucion maligna que sobrevivio 7 anos a su reseccion y cuyos resultados necropsicos mostraron evidencias de recidiva local
Assuntos
Pessoa de Meia-Idade , Humanos , Masculino , Leiomioma , Neoplasias GástricasRESUMO
El presente trabajo actualiza el conocimiento del leiomioblastoma, raro tumor de estirpe muscular lisa que puede observarse en casi todos los organos del tubo digestivo. Su evolucion es lenta y su sintomatologia imprecisa, a veces seudoulcerosa y otras como hemorragia digestiva. Su histologia es muy caracteristica con celulas poliedricas provistas de un halo perinuclear que permite su identificacion precisa. En alrededor del 14% de los casos descriptos presenta evolucion maligna con invasion de organos contiguos con metastasis ganglionares, peritoneales o hepaticas. En sus formas malignas tiene muy lenta evolucion por lo cual el criterio terapeutico, aun con invasion por contiguidad, admite una actitud resectiva amplia con satisfactoria sobrevida. En este trabajo se presenta un caso de evolucion maligna que sobrevivio 7 anos a su reseccion y cuyos resultados necropsicos mostraron evidencias de recidiva local