Lígia Maria Barbosa-Coutinho

Immunohistochemical expression of markers Ki-67, neun, synaptophysin, p53 and HER2 in medulloblastoma and its correlation with clinicopathological parameters

Medulloblastoma (MB) is the most common malignant brain tumor in childhood. The alterations found include: presence of oncoproteins p53 and HER2, elevated mitotic index, and presence of neuronal differentiation. The aim of this study was to determine the immunohistochemical expression of markers Ki-67, NeuN, synaptophysin, HER2 and p53 in 40 MB samples and their correlation with clinicopathologic parameters and survival. In 29 patients (72.5%), >20% of cells were positive for Ki-67. Males showed greater ki-67 expression (p=0.02) and smaller survival rates (p=0.002). NeuN and synaptophysin were negative in 16 (40%) and 8 (20%) cases, respectively. P53 was positive in 18 (45%) cases, with 11 (61%) weakly positive and 7 (39%) strongly positive. HER2 was positive in 23 (57.5%) of the samples and did not show statistical association with survival (p=0.07).

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‐β1, 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.

Meningiomas and hormonal receptors: immunohistochemical study in typical and non-typical tumors

The authors assessed 116 cases of meningiomas classified as typical, atypical and anaplastic and they used an immunohistochemical technique for estrogen and progesterone receptors attempting to determine if there is any difference between typical and non-typical tumors in relation to hormone receptors. The immunohistochemical technique to estrogen receptors was negative in all meningiomas studied. Progesterone receptors were detected in 58.3% of typical, and in 48.2% of non-typical meningiomas. This difference was not statistically significant. However, individually considering the criteria used for selection of non-typical tumours, those that concurrently displayed brain invasion and increased mitotic activity or necrosis, as well as the summation of those three features, were predominantly negative for progesterone receptors (respectively p = 0.038; p = 0.001; and p = 0.044). The authors conclude that estrogen receptors were not present in meningiomas; that progresterone receptors in isolation are not enough to predict a higher tumoral malignancy but can be useful associated with other histological features.

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-α (ERα) 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 ERα 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%. ERα was significantly more prevalent in controls than in patients with adenomas (37.5 versus5.7%; p = 0.001); however, the mean ERα concentration in adenomas was significantly greater than in controls (42.89 versus 0.024%; p < 0.001). No significant difference in the concentration of ERα was found across the clinical presentations, hormonal phenotypes or findings of preoperative CT. Among the ERα-positive adenomas, ERα values were significantly greater in invasive macroadenomas (80%) than in microadenomas (3.33%). MIB-1 values did not differ significantly between ERα-positive and -negative adenomas, nor did the correlation between ERα values and the MIB-1 index attain significance in the total sample, even when only ERα-positive adenomas and positive MIB-1 indexes were considered. It was concluded that, when present in pituitary tumors, ERα exhibits a high concentration, and is more common in nonfunctioning and invasive adenomas, but absent in ACTH-secreting ones.

Expression of nestin and vimentin in gliomatosis cerebri

Gliomatosis cerebri (GC) is a rare form of CNS neoplasia in which there is diffuse involvement of the nervous tissue with or without the presence of tumor mass. The origin of the tumor is unknown, nor whether it represents a disease with diffuse onset or infiltration from a neoplastic focus. Here we studied the histopathologic characteristics of 6 cases with a diagnosis of GC and performed an immunohistochemical analysis using glial fibrillary acidic protein (GFAP), synaptophysin, nestin and vimentin. Most tumor cells were negative for GFAP, even though there were foci of positivity for this marker in all cases. We detected the presence of many positive cells for nestin and vimentin in all studied samples. The presence of these cells may indicate origin of the tumor from undifferentiated cells with a high degree of mobility.

Neuropatologia das epilepsias de difícil controle: estudo de 300 casos consecutivos

We report histopathological findings in 300 consecutive surgical specimens from epilepsy surgery during 6 years. Our material was mainly from temporal lobe epilepsy (70.33%). In 44% the diagnosis was hippocampal sclerosis. There were tumors in 15% of cases and neuronal migration disorders in 10%. The most common tumors were gangliogliomas (42.22%) and dysembryoplastic neuroepithelial tumors (20%). We review the more frequent diagnosis in epilepsy surgery based on this series and comparing with literature.We report histopathological findings in 300 consecutive surgical specimens from epilepsy surgery during 6 years. Our material was mainly from temporal lobe epilepsy (70.33%). In 44% the diagnosis was hippocampal sclerosis. There were tumors in 15% of cases and neuronal migration disorders in 10%. The most common tumors were gangliogliomas (42.22%) and dysembryoplastic neuroepithelial tumors (20%). We review the more frequent diagnosis in epilepsy surgery based on this series and comparing with literature.

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.

Corpora amylacea in temporal lobe epilepsy associated with hippocampal sclerosis

UNLABELLED Hippocampal sclerosis (HS) is the commonest pathology in epileptic patients undergoing temporal lobe epilepsy surgery. Beside, there are an increased density of corpora amylacea (CA) founded in 6 to 63% of those cases. OBJECTIVE verify the presence of CA and the clinical correlates of their occurrence in a consecutive series of patients undergoing temporal surgery with diagnosis of HS. METHOD We reviewed 72 hippocampus specimens from January 1997 to July 2000. Students t test for independent, samples, ANOVA and Tukey test were performed for statistical analysis. RESULTS CA were found in 35 patients (49%), whose mean epilepsy duration (28.7 years) was significantly longer than that group of patients without CA (19.5 years, p=0.001). Besides, when CA were found, duration was also significantly correlated with distribution within hippocampus: 28.7 years with diffuse distribution of CA, 15.4 with exclusively subpial and 17.4 years with distribution subpial plus perivascular (p=0.001). CONCLUSION Our findings corroborate the presence of CA in patients with HS and suggest that a longer duration of epilepsy correlate with a more distribution of CA in hippocampus.

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 (Students 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.

Hemorragia maciça intratumoral em esclerose tuberosa estudo autóptico de um caso

A case of a 13-years-old boy with tuberous sclerosis manifested with the complete syndrome that died with a massive intratumoral hemorrhage is presented. The post mortem examination of the brain disclosed a massive left parenchymatous brain, hemorrhage with intraventricular component. In the hemorrhage, near the lateral ventricle wall, a subependymal giant cell astrocytoma was found. This is the second case in the literature of tuberous sclerosis which cause of death was an intratumoral massive hemorrhage.