RESUMO
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.
Assuntos
Acromegalia/patologia , Adenoma/patologia , Caderinas/análise , Moléculas de Adesão de Célula Nervosa/análise , Neoplasias Hipofisárias/patologia , Fatores de Transcrição da Família Snail/análise , Acromegalia/genética , Acromegalia/metabolismo , Adenoma/química , Adenoma/genética , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/análise , Antígeno CD56/análise , Estudos Transversais , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Neoplasias Hipofisárias/química , Neoplasias Hipofisárias/genética , Reação em Cadeia da Polimerase em Tempo Real , Estatísticas não Paramétricas , Adulto JovemRESUMO
This paper reviews the pathologic features of lesions which are oncocytic and involve classic endocrine organs. The history of the oncocytic cell, its morphologic and ultrastructural features, and important immunohistochemical findings are reviewed. Oncocytic proliferations including non-neoplastic and neoplastic of the thyroid, parathyroid, adrenal (both cortex and medulla), and pituitary are described. Their clinical relevance, functional capacity and capability, and where appropriate, prognostic implications are discussed. Important and relevant molecular biological information is included where appropriate.
Assuntos
Neoplasias do Córtex Suprarrenal/patologia , Células Oxífilas/patologia , Neoplasias Hipofisárias/patologia , Neoplasias da Glândula Tireoide/patologia , Neoplasias do Córtex Suprarrenal/química , Neoplasias do Córtex Suprarrenal/genética , Neoplasias do Córtex Suprarrenal/ultraestrutura , Biomarcadores Tumorais/análise , Humanos , Células Oxífilas/química , Células Oxífilas/ultraestrutura , Neoplasias Hipofisárias/química , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/ultraestrutura , Prognóstico , Neoplasias da Glândula Tireoide/química , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/ultraestruturaRESUMO
Prolactinomas are common benign pituitary neoplasms. Amyloid deposits are rare findings that have been reported in pituitary neoplasms. We report a case of a 48-year old man with a diagnosis of prolactinoma with extensive amyloid deposition. To our knowledge, this is the first case of amyloid in a pituitary neoplasm at our institution.
Assuntos
Amiloide/análise , Neoplasias Hipofisárias/química , Prolactinoma/química , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/patologia , Prolactinoma/patologiaRESUMO
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.
Assuntos
Adenoma/metabolismo , Neoplasias Hipofisárias/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Adenoma/química , Adolescente , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Idoso , Biomarcadores Tumorais , Feminino , Hormônio do Crescimento/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Invasividade Neoplásica , Neoplasias Hipofisárias/química , Prognóstico , Prolactina/metabolismo , Proteína Supressora de Tumor p53/análise , Proteína Supressora de Tumor p53/genéticaRESUMO
We studied the concentration of mRNA from the oncogenes c-myc and c-fos in human pituitary adenomas by Northern blot hybridization (35 somatotrophinomas, 9 prolactinomas, 21 nonsecreting and 3 adrenocorticotrophinomas). The concentration of estrogens and progesterone receptors was also investigated. The levels of c-myc and c-fos mRNA was higher in nonsecreting tumors which were generally the largest and had a higher percentage of recurrence after surgery than the other groups. High concentration of estrogen receptors was observed in tumors derived from cells which are normally the target of this hormone, mainly prolactinomas. They were also present in somatotrophic and nonsecreting adenomas, related to the presence of prolactin or gonadotrophin cells in these tumors. The presence of estrogen receptors indicates that the tumor cells maintain their differentiation and a good prognosis as is the case for prolactinomas. We did not find any relationship between estrogen receptors and the concentration of c-myc and c-fos oncogenes. Larger adenomas (mainly nonsecreting) had higher levels of c-myc and c-fos mRNA than the other tumors and they had an important percentage of recurrence after surgery. It is clear that tumor size is related to the outcome after surgery and that nonsecreting adenomas are usually large because of the late diagnosis. However two large somatotrophinomas with extrasellar expansion also had overexpression of both oncogenes and both relapsed after surgery.