Evaluation of angiogenesis in 77 pituitary adenomas using endoglin as a marker.

Angiogenesis, a fundamental process for the development and growth of a tumor, is less expressive in adenomas than in the normal pituitary tissue. There is controversy about the behavior of angiogenesis as a function of hormonal secretion or other characteristics of pituitary tumors. Endoglin (CD105) is a proliferation-associated antigen on endothelial cells, as well as an endothelial progenitor cell marker. We used the anti-endoglin antibody, a glycoprotein expressed in endothelial cells and conjunctive tissue, as a new marker particularly associated with neovascularization, in order to determine microvascular density (MVD) in pituitary adenomas. There were 77 samples, 31 males and 46 females, carriers of micro- (n = 24) or macroadenomas (n = 53). No significant difference was found in MVD concerning the variables of age, clinical presentation, and immunohistochemical phenotype or tumor size. MVD in males (median 5.4) was significantly higher (P = 0.001) than in females (median 3.0). Cell proliferation, as evaluated by the MIB-1 antibody (a cellular proliferation index [Ki-67 antigen], which is present in all stages of the cellular cycle except for the resting cells), ranged from 0% to 19.58%. No correlation was found between MIB-1 and MVD. It is possible to infer that the lower MVD found in pituitary adenomas in females reflects an inhibitory estrogen action on TGF-beta1, a protein involved in vascular remodeling. Because of its role as a TGF receptor ligand, endoglin proved to be sensitive in detecting this gender difference in pituitary tumor angiogenesis.

Hyperprolactinemia and immunohistochemical expression of intracellular prolactin and prolactin receptor in primary central nervous system tumors and their relationship with cellular replication.

The role of prolactin (PRL) in the CNS remains uncertain. We evaluated the presence of hyperprolactinemia, intracellular prolactin (ICP), and prolactin receptor (PRL-R) in primary CNS tumors, and their relationship with cellular replication with a prospective cross-sectional study of 82 consecutive patients with primary CNS tumors admitted for neurosurgical resection between October 2003 and September 2005. Patients submitted to a questionnaire, and venous blood samples were obtained for measurement of serum PRL and TSH. Immunohistochemical analyses were performed to evaluate the presence of ICP, PRL-R, and Ki-67. Serum PRL levels ranged from 2 to 70 ng/ml, and hyperprolactinemia was detected in 25 cases (30.5%). ICP was detected in 18 patients (21.9%), in whom PRL ranged from 2 to 32 ng/ml. A positive correlation was found between PRL levels and the presence of ICP (Student's t test, P = 0.022). The PRL-R was observed immunohistochemically in 32 cases (39%). The frequencies of hyperprolactinemia, ICP, and PRL-R were similar across the several histological types of CNS tumors. Ki-67 index was similar in all groups. Hyperprolactinemia and intracellular presence of PRL and PRL-R were common findings in this population, suggesting a role for PRL in CNS tumor genesis.

Angiogenesis in craniopharyngiomas: Microvascular density and tissue expression of the vascular endothelial growth factor (VEGF) and endostatin.

Craniopharyngiomas are benign tumors of the sellar region generally associated with endocrine abnormality and often locally aggressive. Several studies have demonstrated that angiogenesis or neovascularization plays an important role in tumoral growth. The microvascular density (MVD) of craniopharyngiomas was determined in tumor tissue samples from a reference neurosurgery center located in southern Brazil using immunohistochemical methods for two endothelial markers, CD34 and CD105 (endoglin). In addition, tissue expression was determined for an angiogenesis stimulatory factor and for one of its inhibitors, the vascular endothelial growth factor (VEGF) and endostatin, respectively. Endothelial cell immunoreactivity for CD34 and CD105 was observed scattered within the stroma. MVD determined using CD105 antigen was significantly lower than the results obtained by using CD34 antigen. There was no association between the two endothelial markers and tumor extension. The epithelial component showed different degrees of immunoreactivity for VEGF and endostatin in all samples analyzed. We were not able to establish a relationship between angiogenesis in craniopharyngiomas and tumor extension with the endothelial markers used in this study. The investigated vascularization stimulatory and inhibitory factors showed no relation with MVD. We believe that CD105 antigen can be a more specific endothelial marker for tumor angiogenesis than CD34 antigen.

Immunohistochemical detection of estrogen receptor alpha in pituitary adenomas and its correlation with cellular replication.

With the aim of evaluating the relationship between pituitary tumorigenesis and the presence of estrogen receptor-alpha (ERalpha) by immunohistochemistry (IH) and their relevance to patients' clinical presentation, hormonal phenotypes of adenomas, preoperative neuroimaging findings, and the index of cellular replication MIB-1, a study was conducted with material from 91 women and 67 men with pituitary adenomas. The patients had acromegaly (29.7%), Cushing's disease (14.6%), hyperprolactinemic syndrome (20.9%), and clinically nonfunctioning tumors (34.8%). Of the patients, 14.6% had microadenomas, 52.5% had macroadenomas with or without suprasellar growth, 28.5% had invasive macroadenomas and in 4.4% the adenoma was not visualized. IH showed that 43 were positive for growth hormone (GH), 16 for corticotropin (ACTH), 18 for prolactin (PRL), 18 for PRL+GH, 6 for luteinizing hormone (LH) and follicle-stimulating hormone (FSH), 15 had a plurihormonal reaction, and 42 had nonfunctioning adenomas. The presence of ERalpha was positive in 9/158 adenomas with a median value for the percentage of labeled cells of 42.89%, and in 6/16 controls (autopsy samples) with a median value for the percentage of labeled cells of 0.024%. ERalpha was significantly more prevalent in controls than in patients with adenomas (37.5 versus 5.7%; p = 0.001); however, the mean ERalpha concentration in adenomas was significantly greater than in controls (42.89 versus 0.024%; p < 0.001). No significant difference in the concentration of ERalpha was found across the clinical presentations, hormonal phenotypes or findings of preoperative CT. Among the ERalpha-positive adenomas, ERalpha values were significantly greater in invasive macroadenomas (80%) than in microadenomas (3.33%). MIB-1 values did not differ significantly between ERalpha-positive and -negative adenomas, nor did the correlation between ERalpha values and the MIB-1 index attain significance in the total sample, even when only ERalpha-positive adenomas and positive MIB-1 indexes were considered. It was concluded that, when present in pituitary tumors, ERalpha exhibits a high concentration, and is more common in nonfunctioning and invasive adenomas, but absent in ACTH-secreting ones.

Alteraçöes encontradas em cérebros de indivíduos acima dos 65 anos e sua correlaçäo com demência de Alzheimer / Changes founs in the brain of people over 65 years old and their correlation with Alzheimer disease

Foram estudadas 12 amostras de cérebros de indivíduos acima de 65 anos. Estas amostras foram submetidas a três técnicas com o objetivo de se detectar placas senis ricas em beta-amilóide: imuno-histoquímica para beta-amilóide; técnica de Glees; técnica de hematoxilina-eosina. Foram detectadas diferenças significativas entre o número de placas encontradas nas diferentes técnicas, o que salienta a possbilidade de diagnósticos falsos-negativos na doença de Alzheimer. A técnica de imuno-histoquímica mostrou-se mais eficiente. Foram submetidos a teste estatístico o número de placas encontradas no córtex e no hipocampo e comparadas, assim como o número de placas encontradas num hemisfério e no outro, sem diferenças significativas. Segue-se a revisäo da literatura quanto aos achados neuropatológicos da doença de Alzheimer, assim como da significancia do nela-amilóide.

Adenomas da hipófise: estudo imuno-histoquímico de 167 casos / Pituitary adenomas: immunohistochemical study of 167 cases

Foram analisados 167 casos de adenomas da hipófise pelo método imuno-histoquímico utilizando o Complexo da Avidina Biotina (ABC) descrito por HSU e col. (1981). Foram usados 6 anti-hormônios hipofisários: anti-prolactina (aPRL), na diluiçäo de 1:1.500, anti-hormônio do crescimento (aHGH), na diluiçäo de 1:4.000, anti-hormônio adrenocorticotrófico (aACTH), na diluiçäo de 1:3.000, anti-hormônio tireotrófico (aTSH), na diluiçäo de trófico (aACTH), na diluiçäo de 1:3.000, anti-hormônio tireotrófico (aTSH), na diluiçäo de 1:3.000, anti-hormônio luteinizante (aLH), na diluiçäo de 1:1.000, anti-hormônio folículo estimulante (a(FSH), na diluiçäo de 1;3.000. O período de incubaçäo foi de 14 a 16 horas a 4-C. Foi realizada também a coloraçäo pelo Orange G-PAS. O levantamento dos dados clínicos, laboratoriais, e radiológicos dos casos de adenomas de hipófise foi realizado após leitura das lâminas pelo método imuno-histoquímico. Dos 167 casos de adenomas da hipófise, 136 (81,4%) mostraram imuno-reaçäo positiva a um ou mais anti-hormônios, variando o índice de positividade entre 1 e 90% das células neoplásicas. A imuno-reaçäo foi positiva exclusivamente a um anti-hormônio em 80 casos (58,8%) e para dois ou mais anti-hormônios nos 56 casos restantes (41,2%), sendo a associaçäo mais freqüentemente encontrada aquela em que a positividade ocorreu para o aPRL e o aHGH. A positividade a reaçäo imuno-histoquímica distribuiu-se da seguinte forma: 100 casos foram positivos para o aPRL, em 49 pacientes de forma isolada; 65 casos foram positivos para o aHGH, em 22 pacientes de forma isolada; 31 casos foram positivos para o aACTH, em 8 pacientes de forma isolada; 5 casos foram positivos ao aTSH, em um paciente de forma isolada; um paciente apresentou adenoma positivo ao aLH; um caso foi positivo ao aFSH