RESUMEN

Pituitary adenomas account for 10-15% of primary intracranial tumors. Growth hormone (GH)-secreting adenomas account for 13% of all pituitary adenomas and cause acromegaly. These tumors can be aggressive, invade surrounding structures and are highly recurrent. The objective of this study was to evaluate E-cadherin, Slug and neural cell adhesion molecule (NCAM) expression in GH-secreting pituitary adenomas and its relationship to tumor invasiveness. A cross-sectional study of patients who underwent hypophysectomy due to GH-secreting pituitary adenoma from April 2007 to December 2014 was carried out. The medical records were reviewed to collect clinical data. Immediately after surgery, tumor samples were frozen in liquid nitrogen and stored in a biofreezer at -80°C for assessment of E-cadherin 1 (CDH1), SLUG (SNAI2), and NCAM (NCAM1) by real-time PCR. The samples were fixed in formalin and embedded in paraffin for immunohistochemical analysis of E-cadherin and NCAM. Thirty-five patients with acromegaly were included in the study. Of these, 65.7% had invasive tumors. Immunohistochemically, E-cadherin was expressed in 96.7% of patients, and NCAM in 80% of patients. There was no statistically significant relationship between tumor grade or invasiveness and immunohistochemical expression of these markers. Regarding gene expression, 50% of cases expressed CDH1, none expressed SNAI2, and 53.3% expressed NCAM1. There was no statistically significant relationship between tumor grade or invasiveness and gene expression of CDH1, SNAI2, and NCAM1. The absence of Slug overexpression and of E-cadherin and NCAM suppression suggests that expression of these markers is not associated with tumor invasiveness in GH-secreting pituitary adenomas.

Asunto(s)

Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Acromegalia/patología , Adenoma/patología , Cadherinas/análisis , Moléculas de Adhesión de Célula Nerviosa/análisis , Factores de Transcripción de la Familia Snail/análisis , Acromegalia/genética , Acromegalia/metabolismo , Inmunohistoquímica , Biomarcadores de Tumor/análisis , Adenoma/genética , Adenoma/química , Expresión Génica , Estudios Transversales , Clasificación del Tumor

RESUMEN

Pituitary adenomas account for 10-15% of primary intracranial tumors. Growth hormone (GH)-secreting adenomas account for 13% of all pituitary adenomas and cause acromegaly. These tumors can be aggressive, invade surrounding structures and are highly recurrent. The objective of this study was to evaluate E-cadherin, Slug and neural cell adhesion molecule (NCAM) expression in GH-secreting pituitary adenomas and its relationship to tumor invasiveness. A cross-sectional study of patients who underwent hypophysectomy due to GH-secreting pituitary adenoma from April 2007 to December 2014 was carried out. The medical records were reviewed to collect clinical data. Immediately after surgery, tumor samples were frozen in liquid nitrogen and stored in a biofreezer at -80°C for assessment of E-cadherin 1 (CDH1), SLUG (SNAI2), and NCAM (NCAM1) by real-time PCR. The samples were fixed in formalin and embedded in paraffin for immunohistochemical analysis of E-cadherin and NCAM. Thirty-five patients with acromegaly were included in the study. Of these, 65.7% had invasive tumors. Immunohistochemically, E-cadherin was expressed in 96.7% of patients, and NCAM in 80% of patients. There was no statistically significant relationship between tumor grade or invasiveness and immunohistochemical expression of these markers. Regarding gene expression, 50% of cases expressed CDH1, none expressed SNAI2, and 53.3% expressed NCAM1. There was no statistically significant relationship between tumor grade or invasiveness and gene expression of CDH1, SNAI2, and NCAM1. The absence of Slug overexpression and of E-cadherin and NCAM suppression suggests that expression of these markers is not associated with tumor invasiveness in GH-secreting pituitary adenomas.

Asunto(s)

Acromegalia/patología , Adenoma/patología , Cadherinas/análisis , Moléculas de Adhesión de Célula Nerviosa/análisis , Neoplasias Hipofisarias/patología , Factores de Transcripción de la Familia Snail/análisis , Acromegalia/genética , Acromegalia/metabolismo , Adenoma/química , Adenoma/genética , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/análisis , Antígeno CD56/análisis , Estudios Transversales , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Neoplasias Hipofisarias/química , Neoplasias Hipofisarias/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Estadísticas no Paramétricas , Adulto Joven

RESUMEN

Meningiomas are common, usually benign tumors of the central nervous system that have a high rate of post-surgical recurrence or regrowth. We determined expression of the proteins merlin, NDRG2, ERBB2, and c-MYC in meningiomas using immunohistochemistry and assessed relationships between protein expression and gender, age, tumor grade, and recurrence or regrowth. The study sample comprised 60 patients, (44 women and 16 men) with a mean age of 53.2 ± 12.7 years. Tumors were classified as grade I (n=48) or grades II and III (n=12). Expression of merlin, NDRG2, ERBB2, and c-MYC was not significantly different statistically with relation to gender, age, or meningioma recurrence or regrowth. Merlin was expressed in 100% of the cases. No statistically significant difference between tumor grade and recurrence or regrowth was identified. Statistically significant differences were identified between the mean age of patients with grade I (54.83 ± 11.60) and grades II and III (46.58 ± 15.08) meningiomas (P=0.043), between strong c-MYC expression and grades II and III (P<0.001), and between partial surgical resection and tumor recurrence or regrowth (P<0.001). These findings reveal the lower mean age among grades II and III meningioma patients than grade I patients, the influence of the protein merlin on tumorigenesis, the association of c-MYC with aggressive meningiomas, and that partial surgical resection is associated with tumor recurrence or regrowth.

Asunto(s)

Neoplasias Meníngeas/metabolismo , Meningioma/metabolismo , Neurofibromina 2/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Receptor ErbB-2/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Adulto , Anciano , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Neoplasias Meníngeas/patología , Meningioma/patología , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia , Factores de Tiempo

RESUMEN

Meningiomas are common, usually benign tumors of the central nervous system that have a high rate of post-surgical recurrence or regrowth. We determined expression of the proteins merlin, NDRG2, ERBB2, and c-MYC in meningiomas using immunohistochemistry and assessed relationships between protein expression and gender, age, tumor grade, and recurrence or regrowth. The study sample comprised 60 patients, (44 women and 16 men) with a mean age of 53.2±12.7 years. Tumors were classified as grade I (n=48) or grades II and III (n=12). Expression of merlin, NDRG2, ERBB2, and c-MYC was not significantly different statistically with relation to gender, age, or meningioma recurrence or regrowth. Merlin was expressed in 100% of the cases. No statistically significant difference between tumor grade and recurrence or regrowth was identified. Statistically significant differences were identified between the mean age of patients with grade I (54.83±11.60) and grades II and III (46.58±15.08) meningiomas (P=0.043), between strong c-MYC expression and grades II and III (P<0.001), and between partial surgical resection and tumor recurrence or regrowth (P<0.001). These findings reveal the lower mean age among grades II and III meningioma patients than grade I patients, the influence of the protein merlin on tumorigenesis, the association of c-MYC with aggressive meningiomas, and that partial surgical resection is associated with tumor recurrence or regrowth.

Asunto(s)

Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Receptor ErbB-2/metabolismo , Neurofibromina 2/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Neoplasias Meníngeas/metabolismo , Meningioma/metabolismo , Factores de Tiempo , Inmunohistoquímica , Estimación de Kaplan-Meier , Clasificación del Tumor , Neoplasias Meníngeas/patología , Meningioma/patología , Recurrencia Local de Neoplasia

RESUMEN

Meningiomas are common, usually benign tumors, with a high postoperative recurrence rate. However, the genesis and development of these tumors remain controversial. We aimed to investigate the presence and implications of a mutated p53 protein and dopamine D2 receptor in a representative series of meningiomas and to correlate these findings with age, gender, tumor grade, and recurrence. Tumor tissue samples of 157 patients diagnosed with meningioma (37 males and 120 females, mean age 53.6±14.3 years) who underwent surgical resection between 2003 and 2012 at our institution were immunohistochemically evaluated for the presence of p53 protein and dopamine D2 receptor and were followed-up to analyze tumor recurrence or regrowth. Tumors were classified as grades I (n=141, 89.8%), II (n=13, 8.3%), or grade III (n=3, 1.9%). Dopamine D2 receptor and p53 protein expression were positive in 93.6% and 49.7% of the cases, respectively. Neither of the markers showed significant expression differences among different tumor grades or recurrence or regrowth statuses. Our findings highlight the potential role of p53 protein in meningioma development and/or progression. The high positivity of dopamine D2 receptor observed in this study warrants further investigation of the therapeutic potential of dopamine agonists in the evolution of meningiomas.

Asunto(s)

Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Infecciones por Enterobacteriaceae/epidemiología , Infecciones por Enterobacteriaceae/microbiología , Centros Médicos Académicos , beta-Lactamasas , Estudios de Casos y Controles , Estudios Transversales , Infecciones por Enterobacteriaceae/etiología , Enterobacteriaceae/genética , Enterobacteriaceae/aislamiento & purificación , Escherichia coli/aislamiento & purificación , Heces/microbiología , Enfermedades Gastrointestinales , Klebsiella/aislamiento & purificación , Cuidados a Largo Plazo , Prevalencia , Pennsylvania/epidemiología , Instituciones Residenciales , Factores de Riesgo

RESUMEN

Meningiomas are common, usually benign tumors, with a high postoperative recurrence rate. However, the genesis and development of these tumors remain controversial. We aimed to investigate the presence and implications of a mutated p53 protein and dopamine D2 receptor in a representative series of meningiomas and to correlate these findings with age, gender, tumor grade, and recurrence. Tumor tissue samples of 157 patients diagnosed with meningioma (37 males and 120 females, mean age 53.6 ± 14.3 years) who underwent surgical resection between 2003 and 2012 at our institution were immunohistochemically evaluated for the presence of p53 protein and dopamine D2 receptor and were followed-up to analyze tumor recurrence or regrowth. Tumors were classified as grades I (n=141, 89.8%), II (n=13, 8.3%), or grade III (n=3, 1.9%). Dopamine D2 receptor and p53 protein expression were positive in 93.6% and 49.7% of the cases, respectively. Neither of the markers showed significant expression differences among different tumor grades or recurrence or regrowth statuses. Our findings highlight the potential role of p53 protein in meningioma development and/or progression. The high positivity of dopamine D2 receptor observed in this study warrants further investigation of the therapeutic potential of dopamine agonists in the evolution of meningiomas.

Asunto(s)

Biomarcadores de Tumor/metabolismo , Neoplasias Meníngeas/metabolismo , Meningioma/metabolismo , Receptores de Dopamina D2/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Adulto , Factores de Edad , Anciano , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Neoplasias Meníngeas/patología , Meningioma/patología , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia , Factores Sexuales , Estadísticas no Paramétricas

RESUMEN

Inactivating mutations of TP53, a tumor suppressor gene, are associated with abnormal cell proliferation. Although p53 expression is common in many human malignancies, p53 protein has seldom been evaluated in pituitary tumors. When detected, the percentage of p53-positive cells is low, and, in general, it is exclusive for invasive lesions. The aim of the present study was to use immunohistochemistry to determine the presence of p53 protein in pituitary adenomas from tumor samples of 163 surgeries performed in 148 patients (40% male, 60% female). In 35% of the cases the adenoma was nonfunctional, while in the others it was associated with PRL, GH and/or ACTH endocrine hypersecretion syndrome. Macroadenomas were observed in 83.2% of the cases with available neuroimage evaluation, of which 28% invaded the cavernous, sphenoid and/or ethmoidal sinus, bone, third ventricle or subfrontal lobe. p53 protein was detected in 2/148 patients (1.3%). Immunohistochemistry was positive for PRL and GH in these cases. Due to the high percentage of invasive pituitary adenomas found in our study, the low frequency of p53 detection suggests that it is inadequate as a routine marker for aggressiveness and as a predictive factor of tumor behavior.

Asunto(s)

Adenoma/metabolismo , Neoplasias Hipofisarias/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Adenoma/química , Adolescente , Hormona Adrenocorticotrópica/metabolismo , Adulto , Anciano , Biomarcadores de Tumor , Femenino , Hormona del Crecimiento/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Mutación , Invasividad Neoplásica , Neoplasias Hipofisarias/química , Pronóstico , Prolactina/metabolismo , Proteína p53 Supresora de Tumor/análisis , Proteína p53 Supresora de Tumor/genética

RESUMEN

Inactivating mutations of TP53, a tumor suppressor gene, are associated with abnormal cell proliferation. Although p53 expression is common in many human malignancies, p53 protein has seldom been evaluated in pituitary tumors. When detected, the percentage of p53-positive cells is low, and, in general, it is exclusive for invasive lesions. The aim of the present study was to use immunohistochemistry to determine the presence of p53 protein in pituitary adenomas from tumor samples of 163 surgeries performed in 148 patients (40 percent male, 60 percent female). In 35 percent of the cases the adenoma was nonfunctional, while in the others it was associated with PRL, GH and/or ACTH endocrine hypersecretion syndrome. Macroadenomas were observed in 83.2 percent of the cases with available neuroimage evaluation, of which 28 percent invaded the cavernous, sphenoid and/or ethmoidal sinus, bone, third ventricle or subfrontal lobe. p53 protein was detected in 2/148 patients (1.3 percent). Immunohistochemistry was positive for PRL and GH in these cases. Due to the high percentage of invasive pituitary adenomas found in our study, the low frequency of p53 detection suggests that it is inadequate as a routine marker for aggressiveness and as a predictive factor of tumor behavior

Asunto(s)

Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Adenoma , Neoplasias Hipofisarias , Proteína p53 Supresora de Tumor , Adenoma , Hormona Adrenocorticotrópica , Biomarcadores de Tumor , Hormona del Crecimiento , Mutación , Invasividad Neoplásica , Neoplasias Hipofisarias , Pronóstico , Prolactina , Proteína p53 Supresora de Tumor