Expression of E-cadherin, Slug and NCAM and its relationship to tumor invasiveness in patients with acromegaly

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.

Expression of E-cadherin, Slug and NCAM and its relationship to tumor invasiveness in patients with acromegaly.

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.

Expression of merlin, NDRG2, ERBB2, and c-MYC in meningiomas: relationship with tumor grade and recurrence.

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.

Expression of merlin, NDRG2, ERBB2, and c-MYC in meningiomas: relationship with tumor grade and recurrence

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.

Abundant immunohistochemical expression of dopamine D2 receptor and p53 protein in meningiomas: follow-up, relation to gender, age, tumor grade, and recurrence

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.

Abundant immunohistochemical expression of dopamine D2 receptor and p53 protein in meningiomas: follow-up, relation to gender, age, tumor grade, and recurrence.

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.

Factors influencing edentulous patients' preferences for prosthodontic treatment.

The aim of this study was to identify factors influencing edentulous patients' preferences for treatment using conventional or implant dentures (ID). A consecutive sample of 112 patients was selected in a university facility. All patients responded to a questionnaire concerning preferences about treatment and factors influencing preferences for conventional complete dentures (CD), implant-retained overdentures (IRO) and fixed implant-supported prostheses (FISP). Subsequently, a set of 21 questions was presented, and patients were requested to rate the importance of various potential reasons influencing their choice of treatment. Preference for CD was more prevalent for maxilla (52·7%) and mandible (41·1%). Fixed implant-supported prostheses and IRO were preferred for the mandible (FISP=37·5%; IRO=21·4%) rather than maxilla (FISP=27·7%; IRO=19·6%). The most preferred treatment option among the subjects when evaluating both arches was the implant-supported fixed or removable prosthesis (FISP/IRO). A preference for combined upper and lower CD was also commonly reported (39·3%). Factor analysis identified six components that accounted for 72·2% of the total variance: (i) psychosocial benefits, (ii) functional performance, (iii) technical and financial concerns, (iv) post-insertion complaints, (v) removability and (vi) longevity. Technical and financial concerns (cost, complexity, surgery risks and duration of treatment) were more relevant for those who preferred ID (P<0·001). With the exception of post-insertion complaints, all mean scores of component factor loadings were positive for ID. Conventional complete dentures are associated with lower expected outcomes by patients, and cost-related issues are the major factors associated with the preferences for implant treatment of edentulous patients.

Combined pituitary hormone deficiency and PROP-1 mutation in two siblings: a distinct MR imaging pattern of pituitary enlargement.

Mutations of the PROP-1 gene are the most frequent genetic defect in patients with combined pituitary hormone insufficiency. We present the cases of 2 siblings with PROP-1 mutations whom we observed longitudinally. Their initial pituitary MR imaging examinations showed identical findings: an enlarged adenohypophysis, with striking hypointensity on T2-weighted images and slight hyperintensity on T1-weighted images. In one of the children, the follow-up MR imaging obtained 3 years after hormonal replacement revealed a decrease in the size of the anterior pituitary lobe.

Measurement of Ki-67 antigen in 159 pituitary adenomas using the MIB-1 monoclonal antibody.

Pituitary adenomas sometimes show rapid growth and recurrence, and about one third invade the structures surrounding the sella turcica. In an attempt to determine aggressive behavior at an early stage, we used the MIB-1 antibody to identify the Ki-67 antigen. The present study was designed to evaluate pituitary adenomatous tissue in terms of secretion and proliferation and to correlate the Ki-67 index with hormone phenotype and invasive behavior. Material from 159 patients submitted to one or more resections of pituitary adenomas was evaluated. Forty-two non-secretory adenomas and 43 adenomas immunoreactive for growth hormone, 19 for prolactin, 18 for growth hormone and prolactin, 16 for adrenocorticotropic hormone (ACTH), and 21 cases of plurihormonal/gonadotropin adenomas were detected by immunohistochemistry. The MIB-1 antibody was positive in 139 samples and the Ki-67 index ranged from 0.16 to 15.48% (mean = 1.22 +/- 2.09%), with no significant difference between genders, age groups, or secretory and non-secretory status. The Ki-67 index was higher in ACTH-secreting adenomas. Invasive pituitary adenomas had a significantly higher Ki-67 index (2.01 +/- 3.15%) than macroadenomas with or without supra-sellar extension (1.12 +/- 1.87%; P = 0.02). The index was not significantly different in the subgroup of adenomas with invasion of the cavernous sinus compared to groups with other types of invasion. We conclude that tumoral proliferative activity evaluated by the detection of the Ki-67 antigen is significantly higher in invasive than noninvasive adenomas, information which can be useful in therapeutic postoperative management since index cut-off values associated with aggressive behavior can be established.

Measurement of Ki-67 antigen in 159 pituitary adenomas using the MIB-1 monoclonal antibody

Pituitary adenomas sometimes show rapid growth and recurrence, and about one third invade the structures surrounding the sella turcica. In an attempt to determine aggressive behavior at an early stage, we used the MIB-1 antibody to identify the Ki-67 antigen. The present study was designed to evaluate pituitary adenomatous tissue in terms of secretion and proliferation and to correlate the Ki-67 index with hormone phenotype and invasive behavior. Material from 159 patients submitted to one or more resections of pituitary adenomas was evaluated. Forty-two non-secretory adenomas and 43 adenomas immunoreactive for growth hormone, 19 for prolactin, 18 for growth hormone and prolactin, 16 for adrenocorticotropic hormone (ACTH), and 21 cases of plurihormonal/gonadotropin adenomas were detected by immunohistochemistry. The MIB-1 antibody was positive in 139 samples and the Ki-67 index ranged from 0.16 to 15.48 percent (mean = 1.22 ± 2.09 percent), with no significant difference between genders, age groups, or secretory and non-secretory status. The Ki-67 index was higher in ACTH-secreting adenomas. Invasive pituitary adenomas had a significantly higher Ki-67 index (2.01 ± 3.15 percent) than macroadenomas with or without supra-sellar extension (1.12 ± 1.87 percent; P = 0.02). The index was not significantly different in the subgroup of adenomas with invasion of the cavernous sinus compared to groups with other types of invasion. We conclude that tumoral proliferative activity evaluated by the detection of the Ki-67 antigen is significantly higher in invasive than noninvasive adenomas, information which can be useful in therapeutic postoperative management since index cut-off values associated with aggressive behavior can be established.

Expression of p53 protein in pituitary adenomas.

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.

Expression of p53 protein in pituitary adenomas

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

Risk factors of neurological lesions in low cervical spine fractures and dislocations.

Eighty-nine patients with lower cervical spine fractures or dislocations were evaluated for risk factors of neurological lesion. The age, sex, level and pattern of fracture and sagittal diameter of the spinal canal were analysed. There were no significant differences on the age, gender, level and Torg's ratio between intact patients and those with nerve root injury, incomplete or complete spinal cord injuries. Bilateral facet dislocations and burst fractures are a significant risk factor of spinal cord injury.

Lipoma of the cerebellopontine angle. Case reports and literature review.

Two patients with cerebellopontine angle (CPA) lipoma were studied. They were submitted to surgical treatment. Available literature was reviewed and 29 cases with same lesion were identified which had been treated by surgery. Clinical manifestations, possibility of diagnostic methods, surgical indications and treatment strategies are discussed. Attention is called to the peculiarities of CPA lipomas and the doubtful validity of attempting complete excision in all cases.

[Macroprolactinoma at 6 years of age: diagnostic difficulties]. / Macroprolactinoma aos 6 anos de idade. Dificuldades diagnósticas.

Prolactinoma is rare in childhood and adolescence. The earliest known diagnosis was reported in a patient at 8 years of age. We report the case of a sellar tumor found in a 6 years old girl. After a long symptomatic period she was brought for treatment. At this time she had partial papillar atrophy, hyperprolactinemia, and diminished reserve of growth hormone and cortisol. Due to rapid visual deterioration, she was submitted to a frontotemporal craniotomy for suspected craniopharyngioma. The tumor tissue immunohistochemistry was positive for prolactin. It is concluded that prolactinoma must be considered in differential diagnosis of sellar tumors in childhood since it benefits from a less aggressive therapy.

[Spontaneous intraparenchymatous hematomas. Experience with 134 cases]. / Hematomas intraparenquimatosos espontâneos. Experiência com 134 casos.

One hundred thirty four cases of spontaneous intraparenchymatous hematomas have been studied. They were separated into six groups according to criteria related to topography, level of consciousness, and hematoma volume. Treatment protocols--conservative, conservative with I.C.P. monitoring, and surgical--were different in each group. Results have shown an increased mortality (p < 0.05) among patients whose level of consciousness were more severely compromised, in those older than 50 years old, and in those harbouring quadrilateral, intraventricular or brainstem hematomas. Overall mortality was 26.1%.

Optic nerve apoplexy caused by a cavernous angioma: case report.

A case of a cavernous angioma of the optic nerve is presented. The abrupt onset of monocular visual symptoms was accompanied by an intense bitemporal headache, indicating apoplexy of the optic nerve. The surgical and histological findings demonstrated a cystic cavernous angioma. The lesion was removed completely without any noticeable bleeding. The preoperative visual deficit persisted.

[Massive intratumor hemorrhage in tuberous sclerosis. Autopsy study of a case]. / Hemorragia maciça intratumoral em esclerose tuberosa. Estudo autóptico de um caso.

A case of a 13-year-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.

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

One hundred and sixty seven cases of pituitary adenoma were analysed using the immunocytochemical method of the Avidin-Biotin Complex (ABC), described by Hsu et al. (1981). Six pituitary anti-hormones were utilized: anti-prolactin (aPRL) at a 1:1,500 dilution; anti-growth hormone (aHGH) at a 1:4,000 dilution: anti-adrenocorticotrophic hormone (aACTH) at a 1:3,000 dilution; anti-thyrothrophic hormone (aTSH) at a 1:3,000 dilution; anti-luteinizing hormone (aLH) at a 1:1,000 dilution; and a anti-follicle-stimulating hormone (aFSH) at a 1:300 dilution. Incubation period was 14 to 16 hours at 4 degrees C. The survey of clinical, laboratory and radiological data of cases of pituitary adenomas was performed after reading the stained slides using the immunocytochemical method. Of the 167 cases of pituitary adenomas, 136 (81.4%) disclosed a positive immunoreaction to one or more anti-hormones, and the positivity index of neoplastic cells varied from 1 to 90%. The immunoreaction was positive exclusively to one anti-hormone in 80 cases (58.8%) and to two or more anti-hormones in 56 cases, and the association most frequently found was between both aPRL and aHGH. The positivity to the immunoreaction was distributed as follows: -100 cases were positive for aPRL, exclusively in 4 cases; -65 cases were positive for aHGH, exclusively in 22 cases; -31 cases were positive for aACTH, exclusively in 8 cases; -5 cases were positive for aTSH, exclusively in one case; -one patient presented an adenoma positive to aLH and another patient to aFSH.

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