Carolina Garcia Soares Leães

Immunohistochemical expression of aromatase and estrogen, androgen and progesterone receptors in normal and neoplastic human meningeal cells

Evidence suggests that sex hormones may play a role in the tumorigenesis of meningiomas, and studies have demonstrated the expression of hormone receptors in these tumors. Aromatase expression has been detected in several normal tissues, including neurons in the CNS, and tumor tissues. We aim to assess the expression of aromatase (ARO) and of progesterone receptor (PR), estrogen receptor (ER) and androgen receptor (AR) in both normal and neoplastic meningeal cells. A cross‐sectional study was conducted with 126 patients diagnosed with meningioma (97 women and 29 men; mean age, 53.6 years) submitted to neurosurgery at Hospital São José, Complexo Hospitalar Santa Casa de Porto Alegre, southern Brazil. Control sections of normal meningeal cells, 19 patients, were obtained by evaluating the arachnoid tissue present in the arachnoid cyst resected material. Immunohistochemistry was applied to assess ARO, PR, ER and AR. Aromatase expression was detected in 100% of the control patients and in 0% of the patients with meningioma. ER was present in 24.6% of the meningiomas and in 0% of the controls, AR in 18.3% of the meningiomas and in 0% of the controls, and PR in 60.3% of the meningiomas and in 47.4% of the controls. A positive association was observed between the presence of AR and ER (OR 3.7; P = 0.01) in meningiomas. There were no significant differences in the presence of hormone receptors between meningioma histological subtypes. PR expression in women with meningioma was significantly higher than that found in men (OR 2.3; P = 0.08). Behavior pattern differences observed between aromatase expression, present in normal tissues and absent in meningiomas, and estrogen and androgen hormone receptors, absent in normal tissues and present in meningiomas, suggest that there is heterogeneity in modulation by sex steroids in the development of these tumors.

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.

Oronasal complications in patients after transsphenoidal hypophyseal surgery

UNLABELLED Transsphenoidal surgery is the most commonly used surgical procedure to handle the hypophyseal region, sometimes associated with oronasal complications. MATERIAL AND METHODS/AIM To evaluate prospectively (specific questionnaire, clinical evaluation) undiagnosed chronic oronasal complications in patients submitted to conventional transsphenoidal adenomectomy surgery, operated at different neurosurgery services more than 6 months ago. RESULTS 49 patients were evaluated, 37/45 presented macroadenoma. 28,5% were submitted to more than one intervention, 2/5 transsphenoidally. Transsphenoidal approach 92.8% through sublabial route. No patient had spontaneous complaint. With the specific questionnaire 63.2% presented complaints. One patient presented an oronasal fistula, 1 stenosis of the nasal valve area with external nasal deformity. Rhinoscopy detected alterations in 77.5%, nasal endoscopy in 87.7%. Septal perforation was present in 10/12 patients with scabs and 2 with purulent secretion. All 4 patients submitted to 2 transsphenoidal approaches presented septal perforation and nasal synechiae. In the endonasal, synechiae (2), alteration in medium meatus (1) and stenosis of the nasal valve area (1) were observed. Only two patients presented normal evaluation. CONCLUSION A high incidence of nasal complications after conventional transsphenoidal surgery observed through examination and not reported spontaneously point to the need of otorhinolaryngological investigation complemented by nasal endoscopy in patients submitted to procedures through this route.

Complicações oronasais em pacientes pós-abordagem hipofisária via transesfenoidal

Transsphenoidal surgery is the most commonly used surgical procedure to handle the hypophyseal region, sometimes associated with oronasal complications. Mate...

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.

Hyperprolactinemia and body weight: prevalence of obesity and overweight in patients with hyperprolactinemia

Abstract Background and objectives: Recent studies have shown an association between prolactin (Prl) levels and body weight, with increased prevalence of obesity in patients with prolactinomas and weight loss associated

Acquired Factor VIII and von Willebrand Factor (aFVIII/VWF) Deficiency and Hypothyroidism in a Case With Hypopituitarism

This article reports a female who presented with bleeding, acquired factor VIII and von Willebrand factor (aFVIII-VWF) deficiency, and central deficiency in the thyroid and adrenal axis (Sheehan’s syndrome). After starting hormone replacement therapy, relief of bleeding manifestations was associated with correction of both FVIII and VWF to normal. This report draws attention to a rare association between the acquired form of von Willebrand disease and hypothyroidism of central origin.

Diastolic function study with conventional and pulsed tissue Doppler echocardiography imaging in acromegalic patients.

Acromegaly is associated with myocardial hypertrophy and it can progress to diastolic and systolic dysfunction. Purpose: To evaluate diastolic function in acromegalic patients through conventional echocardiography (CD) and tissue Doppler imaging (TDI). Methods: Seventeen acromegalic patients were submitted to CD and TDI, and early (E) and atriogenic (A) transmitral flow were evaluated in mitral, septal, and tricuspid regions. Results: In comparison with controls the means of conventional (1.06), septal (1.01), and tricuspid (0.98) E/A ratio were significantly lower in acromegalic patients. E/A ratio <1.0 was demonstrated in 41% and 49% of acromegalics by DC and TDI, respectively, with no statistical difference among the two methods. An inverse linear correlation was shown between mitral E/A ratio and acromegalic age (r =−0.7). Conclusion: In this study, DC and TDI were equally effective in demonstrating diastolic dysfunction, a common finding in acromegalic patients. (ECHOCARDIOGRAPHY, Volume 26, July 2009)

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.

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.