RESUMO
Current guidelines on germline mutation testing for patients suspected of having Lynch syndrome are not entirely clear in patients with tumors demonstrating isolated loss of PMS2 immunohistochemical expression. We analyzed the clinical and pathologic features of patients with tumors demonstrating isolated loss of PMS2 expression in an attempt to (1) determine the frequency of germline MLH1 and PMS2 mutations and (2) correlate mismatch-repair protein immunohistochemistry and tumor histology with germline mutation results. A total of 3213 consecutive colorectal carcinomas and 215 consecutive endometrial carcinomas were prospectively analyzed for DNA mismatch-repair protein expression by immunohistochemistry. In total, 32 tumors from 31 patients demonstrated isolated loss of PMS2 immunohistochemical expression, including 16 colorectal carcinomas and 16 endometrial carcinomas. Microsatellite instability (MSI) polymerase chain reaction was performed in 29 tumors from 28 patients with the following results: 28 tumors demonstrated high-level MSI, and 1 tumor demonstrated low-level MSI. Twenty of 31 (65%) patients in the study group had tumors demonstrating histopathology associated with high-level MSI. Seventeen patients underwent germline mutation analysis with the following results: 24% with MLH1 mutations, 35% with PMS2 mutations, 12% with PMS2 variants of undetermined significance, and 29% with no mutations in either MLH1 or PMS2. Three of the 4 patients with MLH1 germline mutations had a mutation that results in decreased stability and quantity of the MLH1 protein that compromises the MLH1-PMS2 protein complex, helping to explain the presence of immunogenic but functionally inactive MLH1 protein within the tumor. The high frequency of MLH1 germline mutations identified in our study has important implications for testing strategies in patients suspected of having Lynch syndrome and indicates that patients with tumors demonstrating isolated loss of PMS2 expression without a germline PMS2 mutation must have MLH1 mutation analysis performed.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Adenosina Trifosfatases/deficiência , Biomarcadores Tumorais/deficiência , Biomarcadores Tumorais/genética , Carcinoma/química , Carcinoma/genética , Neoplasias Colorretais Hereditárias sem Polipose/química , Neoplasias Colorretais Hereditárias sem Polipose/genética , Enzimas Reparadoras do DNA/deficiência , Proteínas de Ligação a DNA/deficiência , Neoplasias do Endométrio/química , Neoplasias do Endométrio/genética , Mutação em Linhagem Germinativa , Imuno-Histoquímica , Proteínas Nucleares/genética , Proteínas Adaptadoras de Transdução de Sinal/análise , Adulto , Idoso , Biópsia , Carcinoma/patologia , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Reparo de Erro de Pareamento de DNA , Análise Mutacional de DNA , Neoplasias do Endométrio/patologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento , Proteína 1 Homóloga a MutL , Proteínas Nucleares/análise , Fenótipo , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Estudos ProspectivosRESUMO
OBJECTIVE: To evaluate p53 protein expression in the endometrial polyp and compare with adenocarcinoma and atrophic endometrium of postmenopausal women. MATERIALS AND METHODS: Ninety-eight postmenopausal women were included in this study and divided into three groups related to histopathologic diagnosis: Group A--endometrial adenocarcinoma (n = 40), Group B--endometrial polyp (n = 38), and Group C--endometrial atrophy (n = 20). The length of this study was from 1990 to 2004. The endometrial samples were collected from hysteroscopic biopsy or surgery then processed for histopathologic routine. One thousand cells of each histological section were evaluated for immunohistochemical analysis using p53 antibodies. The ANOVA test was performed for the statistical analysis. RESULTS: The expression of p53 in adenocarcinoma samples was the highest. The expression of polyp was positive when associated to hyperplasia without atypia. All samples of atrophic endometrial were negative. CONCLUSIONS: The present data suggested that presence of hyperplasia in the endometrial polyp is factor to increase the expression of p53.
Assuntos
Adenocarcinoma/química , Biomarcadores Tumorais/análise , Neoplasias do Endométrio/química , Endométrio/química , Endométrio/patologia , Pólipos/química , Proteína Supressora de Tumor p53/análise , Doenças Uterinas/metabolismo , Idoso , Atrofia/metabolismo , Biomarcadores Tumorais/metabolismo , Hiperplasia Endometrial/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Pólipos/patologia , Pós-Menopausa/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND: The endometrium is a very dynamic organ that experience several half-full processes by the ovarian secretion of estradiol and progesterone. The effect of hormones steroids, in the epithelial cells, endoteliales and estromales of the endometrium, is influenced by receptors of estrogens and progesterone. OBJECTIVE: determine if there are any differences in the density of the estrogen receptors (ER) between the normal endometrial, the simple and complex hyperplasia, the atypical hyperplasia and the. MATERIAL AND METHODS: A retrospective study comparative was made. We included 143 samples that were knit together in 5 categories of the following way: Normal endometrial (n = 38), Simple hyperplasia (n = 58), Complex hyperplasia (n = 22), Atypical hyperplasia (n = 9), Adenocarcinoma (n = 16). Immunohistochemistry method was used through estreptavidin biotin peroxidase diaminobenzidine. The samples were analyzed for computer image. Mendez modified technique for cell count was used. The statistical analysis included descriptive statistical. The differences between groups were analyzed using ANOVA-MANOVA and t of Student for independent samples (alpha = 0.05) and other statistical test. RESULTS: there were no statistical significant differences on the cell density with ER between the normal endometrial and the simple and complex hyperplasia. The estrogen receptors are decreased in the atypical hyperplasia and the endometrial adenocarcinoma. DISCUSSION: The gravity of the injury increases proportionally with the age; the most important factor in the reduction of the cells with estrogénicos receivers is the neoplastic transformation.
Assuntos
Adenocarcinoma/química , Neoplasias do Endométrio/química , Receptores de Estrogênio/análise , Hiperplasia Endometrial , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
We report on an unusual endometrial polyp in a postmenopausal woman taking tamoxifen for 7 years after surgical resection of a breast carcinoma. A 63-year-old woman with endometrial thickening was submitted to hysteroscopy with biopsy, which revealed a polyp with a sex cord-like pattern. The hysterectomy specimen showed florid adenomyosis, and in the background, there were rare sex cord-like foci. Immunohistochemistry can be useful in differentiating sex cord-like elements from metastatic breast cancer to endometrium. This is, to our knowledge, the first observation in literature correlated to tamoxifen intake.
Assuntos
Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/patologia , Pólipos/patologia , Tumores do Estroma Gonadal e dos Cordões Sexuais/patologia , Antígeno 12E7 , Antígenos CD/análise , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Moléculas de Adesão Celular/análise , Terapia Combinada , Neoplasias do Endométrio/química , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Pólipos/química , Pólipos/diagnóstico , Tumores do Estroma Gonadal e dos Cordões Sexuais/química , Tumores do Estroma Gonadal e dos Cordões Sexuais/diagnóstico , Tamoxifeno/efeitos adversos , Tamoxifeno/uso terapêutico , Vimentina/análiseRESUMO
Estrogen and progestin combination in hormone replacement therapy (HRT) increases the incidence of breast cancer, but decreases the endometrial cancer risk of unopposed estrogen. Therefore, a SERM such as Tibolone, that delivers the beneficial, but not the adverse side effects, of steroid hormones would be clinically advantageous. However, data from the Million Women Study suggests that Tibolone increases the risk of both breast and endometrial cancer. Herein, we assessed the estrogenic and progestagenic actions of Tibolone using transvaginal sonography studies and an in vitro model of breast (ZR-75, MCF7) and endometrial cancer (Ishikawa). The known cancer associated proteins (ER, EGFR, STATS, tissue factor and Bcl-xL) were selected for study. Transvaginal sonography demonstrated that postmenopausal women treated with Tibolone displayed a thinner endometrium than in the late proliferative phase, but had a phenotype characteristic of the secretory phase, thus demonstrating the estrogenic and progestagenic actions of this SERM. In vitro, Tibolone acted as an estrogen in downregulating ER and upregulating Bcl-xL, yet as progesterone, increasing STAT5 and tissue factor in breast cancer cells. The increase in tissue factor by Tibolone correlated with its coagulative potential. Interestingly, EGFR was up-regulated by progesterone in the breast and by estrogen in endometrial cells, while Tibolone increased protein levels in both cell types. In conclusion, this study further demonstrates the estrogenic and progestagenic nature of Tibolone. The pattern of regulation of known oncogenes in cells of breast and endometrial origin dictates caution and vigilance in the prescription of Tibolone and subsequent patient monitoring.
Assuntos
Biomarcadores Tumorais/análise , Endométrio/efeitos dos fármacos , Moduladores de Receptor Estrogênico/farmacologia , Estrogênios/metabolismo , Norpregnenos/farmacologia , Progestinas/metabolismo , Western Blotting , Neoplasias da Mama/química , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Neoplasias do Endométrio/química , Neoplasias do Endométrio/genética , Endométrio/diagnóstico por imagem , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Fatores de Tempo , UltrassonografiaRESUMO
The progesterone receptor contents in the cytosol of two of three samples of same tumor was measured in 19 cases of endometrial cancer. The receptor concentration in one sample of each tumor was calculated by Scatchard analysis of specific binding data; in the other, one or two samples of each tumor, the receptor concentration was calculated by using a single point. All tumors did have receptors at least in one of the two or three samples. Ten tumors showed certain consistency in the receptor content in the two or three samples. On the other hand, a striking variability in the receptor content between the two or three samples of each of the remaining tumors was found, ranging from zero to several hundred femtomoles/mg of protein. In seven cases, follow-up was possible during 66 months, and the response to progestagen treatment was independent from the progesterone-receptor content. Our results suggest that the analysis of a single site of a tumor would reveal values that might not be representative of the tumor and, furthermore, it would explain, at least partially, the uncertain response to progestagen therapy that has been frequently described.
Assuntos
Adenocarcinoma/química , Neoplasias do Endométrio/química , Receptores de Progesterona/análise , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Idoso , Biópsia , Citosol/metabolismo , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/mortalidade , Feminino , Histocitoquímica , Humanos , Pessoa de Meia-Idade , Progestinas/uso terapêutico , Prognóstico , Receptores de Progesterona/metabolismoRESUMO
Se analizó el contenido de receptores de progesterona en el citosol de dos o tres muestras obtenidas del mismo tumor, en 19 casos de cáncer endometrial. La concentración de receptores en una muestra de cada tumor fue obtenida por análisis de Scatchard; en la otra o las otras dos muestras de cada tumor, la concentración de receptores fue calculada a parir de un solo punto. Todos los tumores tuvieron receptores al menos en una de las dos o tres muestras. Diez tumores mostraron cierta consistencia en el contenido de receptores las dos o tres muestras de los nueve tumores restantes, con un rango que va desde cero hasta varios cientos de femtomoles/mg de proteína. En siete casos, en que se pudo seguir la evolución de las pacientes hasta por un período de 66 meses, encontramos que la magnitud de respuesta a progestágenos fue independiente del contenido de receptores de progesterona. Estos resultados hacen pensar que el análisis de un sólo sitio de tumor endometrial revelaría valores que pudieran no ser representativos del tumor total, lo cual explicaría, al menos parcialmente, la respuesta incierta que frecuentemente se obtiene en la terapia progestacional