RESUMO
INTRODUCTION: Prolactin (PRL) binds its receptor (PRLR) and stimulates cell proliferation, differentiation and survival in prostate cancer (PCa) cell lines via STAT5a, MAPK and AKT. OBJECTIVE: To evaluate the expression of PRL and PRLR in normal and tumor prostate tissues with different Gleason patterns. METHODS: Samples of normal, benign prostatic hyperplasia and PCa with different Gleason patterns were selected from radical prostatectomy. The intensity, location and percentage of stained cells for PRL and PRLR were evaluated by Immunohistochemistry. Co-localization was observed by confocal microscopy. RESULTS: PRL was expressed diffusely and with a mild intensity in the cytoplasm of normal and tumor prostate luminal cells. Its expression only augmented in the Gleason 3 pattern (p< 0.0001). The immunostaining intensity and the percentage of positive cells for PRLR did not vary between normal and tumor tissues. However, the location of the PRLR was modified by the tumorigenic process.In non-tumor tissues, PRLR expression was mostly in plasma membrane in the apical zone of epithelial cells. In tumor tissues, it was expressed in intracellular vesicles.The co-localization of PRL and PRLR was demonstrated in normal and tumor tissues suggesting that PRL could be acting in an autocrine and paracrine manner. CONCLUSION: PRL and its receptor were present in the cytoplasm of the epithelial cells of the normal and tumor prostate gland. In tumor tissues, the change in the location and appearance of cryptic PRLRs that store PRL may keep active the different signaling pathways related to cell proliferation and survival.
INTRODUCCIÓN: La prolactina (PRL) se une a su receptor (PRLR) y estimula la proliferación celular, la diferenciación y la supervivencia de la líneas celulares de cáncer de próstata vía STAT5a, MAPK y AKT.OBJETIVO: Evaluar la expresión de la PRL y PRLR en tejido normal y tejido de cáncer de próstata con varios patrones de Gleason.MÉTODOS: Se seleccionaron muestras de tejido benigno, hiperplasia y cáncer de próstata con diferentes patrones de Gleason de prostatectomías radicales. La intensidad, localización y porcentaje de células teñidas por PRL y PRLR fueron evaluadas por immunohistoquimica. La co-localización se observó con microscopio confocal.RESULTADOS: PRL se presentó de forma difusa y con intensidad media en el citoplasma de células luminales normales y de tumor prostático. La expresión solamente aumentó en patrón Gleason 3 (p<0,0001). La intensidad de la tinción immunohistoquímica y el porcentaje de células positivas para PRLR no varió entre células normales y tejidos tumorales. Pero, la localización del PRLR fue modificada por el proceso generador del tumor. En tejidos no-tumorales, la expresión de PRLR fue sobre todo en la membrana plasmática en la zona apical de las células epiteliales. En tejidos tumorales, se presentó en las vesículas intracelulares. La co-localizacion de la PRL y PRLR se demostró en tejido normal y tumoral sugeriendo que la PRL funciona con un efecto autocrino y paracrino.CONCLUSIÓN: La PRL y su receptor estuvieron presentes en el citoplasma de células epiteliales de tejido normal y glándula prostática tumoral. En tejidos tumorales, el cambio de localización y la apariencia cripticas del PRLR que guarda la PRL debe mantener activos los diferentes caminos de señalización relacionados con la proliferación celular y la supervivencia.
Assuntos
Neoplasias da Próstata , Receptores da Prolactina , Humanos , Masculino , Prolactina , Transdução de SinaisRESUMO
OBJECTIVE: Hemoxigenase 1 (HO-1) is an enzyme that has anti-apoptotic and proliferative effects on tumor cells. However, there is little epidemiological and clinical evidence on the role of HO-1 in urologic tumors. OBJECTIVE: To determine if there is correlation between the expression of HO-1 and the histological characteristics, evolution, Disease Free Survival (DFS) and cancer mortality in Clear Cell Renal Cell Carcinoma (cRCC). MATERIALS AND METHODS: A retrospective study including 34 patients (9 women and 25 men) with cRCC from the "Servicio de Urología del Policlínico Neuquén" (Argentina) throughout 2003-2008. The expression of HO-1 by Immunohistochemistry (IHC) was determined. The statistical analysis was performed using the Student'sT test and Pearson correlation coefficient (p≤0.05). RESULTS: HO-1 was expressed in the epithelial cells of the tubules from normal kidney tissue and in the cytoplasmof cRCC tumor cells. There were no differences in the HO-1 expression related to the gender, age, tumorsize, stage of disease and 5 years DFS. High FuhrmancRCC had a greater expression of HO-1 compared with low Fuhrman cRCC (p≤0.05). The score of immunostaining for HO-1 was greater in those tumors located in the mesorrenal area, which coincidentally presented a more advanced stage of the disease. CONCLUSIONS: Over expression of HO-1 in tumors located in the interpolar zone and with high Furhman grade suggest that HO-1 could be a good adjunctive marker for the aggressiveness of the cRCC.
OBJETIVO: Hemoxigenasa 1 (HO-1) es una enzima que tiene efectos antiapoptóticos y proliferativos en células tumorales. Sin embargo, existe poca evidencia epidemiológica y clínica sobre el rol de la HO-1 en los tumores urológicos. Objetivo: determinar si existe correlación entre la expresión de HO-1 y las características histológicas, evolución, Sobrevida Libre de Enfermedad (SLE) y mortalidad por cáncer en Carcinomas Renales de Células Claras (cRCC). MATERIALES Y MÉTODOS: Se realizó un estudio retrospectivo en 34 pacientes (9 mujeres y 25 hombres) con cRCC del Servicio de Urología del Policlínico Neuquén, reclutados entre los años 2003 y 2008. Se determinó la expresión de HO-1 por Inmunohistoquímica (IHQ). El análisis estadístico se realizó mediante la prueba T de Student y Coeficiente de correlación de Pearson (p<0,05). RESULTADOS: HO-1 se expresó en el epitelio de los túbulos del tejido renal normal y en el citoplasma de las células tumorales de cRCC. No se observaron diferencias en la expresión de HO-1 según género, edad, tamaño tumoral, estadio de la enfermedad y SLE a los 5 años. Los tumores con Fuhrman alto presentaron una mayor expresión de HO-1 que los Furhman bajo (p≤0,05). El score de inmunotinción de HO-1 fue mayor en los tumores localizados en la zona interpolar, que coincidentemente presentaban un estadio más avanzado de la enfermedad. CONCLUSIONES: La sobreexpresión de HO-1 en tumores localizados en la zona interpolar y con grado de Furhman alto sugieren que HO-1 podría ser un buen marcador complementario de la agresividad del cRCC.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Pré-Escolar , Feminino , Heme Oxigenase-1 , Humanos , Imuno-Histoquímica , Masculino , Prognóstico , Estudos RetrospectivosRESUMO
Mutation of the mismatch repair genes MLH1 and MSH2 account for the majority of the genetic abnormalities in Lynch syndrome. Immunohistochemical detection of their protein products is becoming an increasingly common method to detect these mutations. The aim of this study was to compare the expression of MLH1 and MSH2 by immunohistochemistry and its relationship with a group of clinical and histological variables in patients with known Lynch syndrome (n=16) and in cohort of young patients (less than 50 years) who did not meet Amsterdam criteria (n=25). The mean age was 40.7 and 64% were women. Conclusive results were obtained in 40 cases (97.6%). Eighteen cases (45%) showed abnormal expression of either MLH1 (11 cases) or MSH2 (6 cases) and both stains (1 case). Alteration of the normal staining pattern was seen more commonly in patients with Lynch syndrome than in the sporadic group (68.7% vs 28%, p=0.01). A significant correlation was obtained between abnormal protein expression and microsatellite instability (MSI): normal expression: 5.9%, lack of expression: 92.3%, p<0.0001. The sensitivity and specificity of the immunohistochemical to predict MSI were 92.3% and 94.1% respectively. Immunohistochemistry and MSI results did not correlate with any histopathological parameter. In conclusion, in our experience abnormal staining of MLH and MSH correlates strongly with the presence of MSI. In addition it appears that in our population a significant proportion of young patients (< 50 years old) demonstrate alterations in the mismatch repair gene products suggesting an important role of these molecules in tumorigenesis.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais/genética , Reparo de Erro de Pareamento de DNA , Instabilidade de Microssatélites , Proteína 2 Homóloga a MutS/genética , Proteínas Nucleares/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adolescente , Adulto , Idoso , Neoplasias Colorretais/patologia , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/metabolismo , Proteínas Nucleares/metabolismo , Reação em Cadeia da PolimeraseRESUMO
Las mutaciones de los genes MLH1 y MSH2 son frecuentemente implicadas en el síndrome de Lynch. La expresión inmunohistoquímica (IHQ) es una forma simple de selección para pruebas moleculares. Se analizó la IHQ de MLH1 y MSH2 en pacientes con síndrome de Lynch (16 casos) y pacientes menores de 50 años sin antecedentes familiares (25 casos). Se estudiaron 41 tumores de un grupo de pacientes (64% mujeres) de edad promedio 40.7 años (rango: 16-75). Se obtuvieron resultados concluyentes en 40 casos (97.6%). Dieciocho casos (45%) presentaron falta de expresión (MLH1 negativa: 11 casos; MSH2 negativa: 6 casos; MLH1 negativa y MSH2 negativa: 1 caso), con una incidencia significativamente mayor en pacientes con síndrome de Lynch (68.7% vs. 28%, p=0.01). Entre los casos esporádicos, 5 casos (20%) mostraron falta de expresión MLH1 y 2 casos (8%) con falta de expresión MSH2. La falta de expresión IHQ presentó una fuerte asociación con inestabilidad microsatelital alta (IMS): expresión normal: 5.9%, expresión negativa: 92.3%, P<0.0001. Los índices de sensibilidad y especificidad de la IHQ para detectar IMS fueron de 92.3% y 94.1% respectivamente. Los patrones de IHQ y de IMS no se relacionaron a ninguna característica histopatológica. En conclusión, el análisis inmunohistoquímico de las proteínas MLH1 y MSH2 fue altamente sensible y específico para detectar IMS y permitió identificar en un 45% de los casos la proteína alterada. El índice de falta de expresión IHQ entre los casos esporádicos diagnosticados antes de los 50 años justifica su implementación sistemática en este grupo de pacientes.
Mutation of the mismatch repair genes MLH1 and MSH2 account for the majority of the genetic abnormalities in Lynch syndrome. Immunohistochemical detection of their protein products is becoming an increasingly common method to detect these mutations. The aim of this study was to compare the expression of MLH1 and MSH2 by immunohistochemistry and its relationship with a group of clinical and histological variables in patients with known Lynch syndrome (n=16) and in cohort of young patients (less than 50 years) who did not meet Amsterdam criteria (n=25). The mean age was 40.7 and 64% were women. Conclusive results were obtained in 40 cases (97.6%). Eighteen cases (45%) showed abnormal expression of either MLH1 (11 cases) or MSH2 (6 cases) and both stains (1 case). Alteration of the normal staining pattern was seen more commonly in patients with Lynch syndrome than in the sporadic group (68.7% vs 28%, p=0.01). A significant correlation was obtained between abnormal protein expression and microsatellite instability (MSI): normal expression: 5.9%, lack of expression: 92.3%, p<0.0001. The sensitivity and specificity of the immunohistochemical to predict MSI were 92.3% and 94.1% respectively. Immunohistochemistry and MSI results did not correlate with any histopathological parameter. In conclusion, in our experience abnormal staining of MLH and MSH correlates strongly with the presence of MSI. In addition it appears that in our population a significant proportion of young patients (< 50 years old) demonstrate alterations in the mismatch repair gene products suggesting an important role of these molecules in tumorigenesis.