Browsing by Author "Silva, AI"
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- ABCA 3 mutation on a Portuguese female infant with respiratory distress syndrome (RDS): a case-reportPublication . Ferreira, M; Gonçalves, JP; Cruz, M; Silva, AI; Teixeira, M; Pardal, F
- Association between functional EGF+61 polymorphism and glioma riskPublication . Costa, BM; Ferreira, P; Costa, S; Canedo, P; Oliveira, P; Silva, AI; Pardal, F; Suriano, G; Machado, JC; Lopes, JM; Reis, RMPURPOSE: Epidermal growth factor (EGF) plays a critical role in cancer. A polymorphism in the EGF gene (EGF+61) may influence its expression and contribute to cancer predisposition and aggressiveness. In the present study, we aimed to elucidate the role of EGF+61 in glioma susceptibility and prognosis. EXPERIMENTAL DESIGN: A case-control study involving 197 glioma patients and 570 controls was done. Univariate and multivariate logistic regression analyses were used to calculate odds ratio (OR) and 95% confidence intervals (95% CI). False-positive report probability was also assessed. The luciferase reporter gene assay was used to ascertain the functional consequences of this polymorphism. RESULTS: Corroborating the univariate analysis, the multivariate model showed that the G allele conferred higher risks for gliomas (OR, 1.32; 95% CI, 1.04-1.67), glioblastomas (OR, 1.47; 95% CI, 1.02-2.10), and oligodendrogliomas (OR, 1.55; 95% CI, 1.07-2.23). The GG genotypes were associated with increased risk for gliomas (OR, 1.71; 95% CI, 1.07-2.73), glioblastomas (OR, 2.03; 95% CI, 1.02-4.05), and oligodendrogliomas (OR, 2.72; 95% CI, 1.18-6.28). In addition, the AG+GG genotypes were associated with higher risk for gliomas (OR, 1.52; 95% CI, 1.03-2.23) and oligodendrogliomas (OR, 2.80; 95% CI, 1.35-5.79). No significant association was observed between the EGF+61 polymorphism and glioblastoma or oligodendroglioma patients' overall survival. The luciferase reporter gene assay exhibited a significant increased promoter activity for the G variant compared with the reference A allele. CONCLUSIONS: These findings support the role of the EGF+61 polymorphism as a susceptibility factor for development of gliomas and show its implication on EGF promoter activity.
- Cisto epidermoide intracraniano com transformação maligna catorze anos após o diagnóstico inicialPublication . Ferreira, M; Silva, AI
- Expression, mutation and copy number analysis of platelet-derived growth factor receptor A (PDGFRA) and its ligand PDGFA in gliomasPublication . Martinho, O; Longatto-Filho, A; Lambros, MB; Martins, A; Pinheiro, C; Silva, AI; Pardal, F; Amorim, J; Mackay, A; Milanezi, F; Tamber, N; Fenwick, K; Ashworth, A; Reis-Filho, J; Lopes, JM; Reis, RMBACKGROUND: Malignant gliomas are the most prevalent type of primary brain tumours but the therapeutic armamentarium for these tumours is limited. Platelet-derived growth factor (PDGF) signalling has been shown to be a key regulator of glioma development. Clinical trials evaluating the efficacy of anti-PDGFRA therapies on gliomas are ongoing. In this study, we intended to analyse the expression of PDGFA and its receptor PDGFRA, as well as the underlying genetic (mutations and amplification) mechanisms driving their expression in a large series of human gliomas. METHODS: PDGFA and PDGFRA expression was evaluated by immunohistochemistry in a series of 160 gliomas of distinct World Health Organization (WHO) malignancy grade. PDGFRA-activating gene mutations (exons 12, 18 and 23) were assessed in a subset of 86 cases by PCR-single-strand conformational polymorphism (PCR-SSCP), followed by direct sequencing. PDGFRA gene amplification analysis was performed in 57 cases by quantitative real-time PCR (QPCR) and further validated in a subset of cases by chromogenic in situ hybridisation (CISH) and microarray-based comparative genomic hybridisation (aCGH). RESULTS: PDGFA and PDGFRA expression was found in 81.2% (130 out of 160) and 29.6% (48 out of 160) of gliomas, respectively. Its expression was significantly correlated with histological type of the tumours; however, no significant association between the expression of the ligand and its receptor was observed. The absence of PDGFA expression was significantly associated with the age of patients and with poor prognosis. Although PDGFRA gene-activating mutations were not found, PDGFRA gene amplification was observed in 21.1% (12 out of 57) of gliomas. No association was found between the presence of PDGFRA gene amplification and expression, excepting for grade II diffuse astrocytomas. CONCLUSION: The concurrent expression of PDGFA and PDGFRA in different subtypes of gliomas, reinforce the recognised significance of this signalling pathway in gliomas. PDGFRA gene amplification rather than gene mutation may be the underlying genetic mechanism driving PDGFRA overexpression in a portion of gliomas. Taken together, our results could provide in the future a molecular basis for PDGFRA-targeted therapies in gliomas.
- Galectin-3 expression is ubiquitous in tumors of the sellar region, nervous system, and mimics - An immunohistochemical and RT-PCR studyPublication . Rodriguez, FJ; Scheithauer, BW; Roncaroli, F; Silva, AI; Kovacs, K; Brat, DJ; Jin, LGalectin-3 expression has been reported in spindle cell oncocytoma, certain pituitary adenoma subtypes, astrocytomas, oligodendrogliomas, and meningiomas. We evaluated galectin-3 protein expression by immunohistochemistry in 201 cases of a variety of nervous system and sellar tumors, as well as mRNA expression by reverse transcription-polymerase chain reaction in formalin-fixed paraffin-embedded tissue in a subset (20 cases). Immunohistochemical results were evaluated in a semiquantitative fashion on a 4-tiered scale (0 to 3). Strong (3+) immunoreactivity was seen in most of the cases (61%), followed by 2+(22%), and 1+(13%) staining. Only 4% of the lesions studied were immunonegative. Galectin-3 mRNA was present in 15 of the 18 cases (83%) in which reverse transcription-polymerase chain reaction was successful. Significant differences in protein expression were noted in the following 2 settings: specific meningioma subtypes (P=0.004, Fisher exact test) wherein clear cell meningioma demonstrated weak protein expression when compared with other meningioma variants. No significant difference was noted with respect to World Health Organization grade. Galectin-3 was also strongly expressed in benign nerve sheath tumors but only moderately expressed in malignant peripheral nerve sheath tumors (P=0.0009, Fisher exact test). Although galectin-3 positivity is a key feature of the immunophenotype of spindle cell oncocytoma, its consistent expression in other morphologically similar tumors (meningioma, pituicytoma, nerve sheath tumors, granular cell tumor, metastases) makes it of little use in the differential diagnosis of sellar region tumors, a setting in which it should be discouraged. Diagnostic uses of this marker may be limited to specific settings, including some meningioma subtypes and nerve sheath tumors.
- Ganglioglioma of the neurohypophysisPublication . Scheithauer, BW; Silva, AI; Parisi, JE; Kovacs, K; Horvath, EThe normal infundibulum and neurohypophysis consist entirely of neuronal processes, the neuronal cell bodies of which lie within the supraoptic and paraventricular nuclei of the hypothalamus and supportive glial cells or pituicytes. The finding of neurons within the neurohypophysis is exceedingly rare, as are ganglion cell tumors at this site. In this paper, we report a ganglion cell tumor of the neurohypophysis found incidentally at autopsy. Despite chronic hypertension and the finding of some vasopressin immunoreactivity in lesional neurons, the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was excluded on the basis of normal serum sodium levels. The morphologic and immunohistochemical features of the tumor are presented, cytogenetic considerations are discussed, and literature regarding neuronal lesions of the pituitary gland is reviewed
- Ganglioneuroma da Supra-renal – relato de caso clínicoPublication . Monteiro, AM; Alves, M; Souto, S; Luís, D; Silva, AI; Marques, OINTRODUÇÃO Os ganglioneuromas da supra-renal são tumores raros, benignos, bem diferenciados e têm origem na crista neural. A maioria dos doentes com ganglioneuroma da supra-renal são assintomáticos, e grande parte destes tumores são não secretores. Geralmente, são encontrados acidentalmente em exames de imagem abdominal por outro motivo. CASO CLÍNICO Sexo feminino, 53 anos, com antecedentes de hipertensão arterial diagnosticada aos 30 anos, dislipidémia, patologia depressiva e histerectomia por prolapso uterino. Medicada habitualmente com espironolactona, cloreto de potássio, atorvastatina, omeprazol, fluoxetina e lorazepam. Antecedentes de internamentos de repetição em serviço de Medicina Interna por hipocaliémia recorrente. Referenciada à consulta de Endocrinologia por suspeita de hiperaldosteronismo primário. Apresentava nódulo na supra-renal diagnosticado em contexto de estudo da hipertensão arterial e hipocaliémia. Clínica de astenia, anorexia, cãimbras e dores musculares com alguns meses de evolução. Sem alterações relevantes ao exame objectivo. A TC das supra-renais revelava “supra-renal esquerda com nódulo hipodenso de 3 cm, eventual adenoma”. A RM abdomino-pélvica mostrou: “supra-renal esquerda com massa quística complexa, com parede espessa (3-5mm de espessura parietal), onde se identifica um nódulo mural com ~11x7mm, questionando-se a possibilidade de degenerescência quística tumoral/pseudoquisto, sendo de ponderar a sua exérese cirúrgica.” O estudo funcional do nódulo foi normal. Foi submetida a suprarrenalectomia esquerda por via laparoscópica. O exame histológico revelou um ganglioneuroma. Foi referenciada a consulta de Nefrologia para investigação da hipocaliémia, tendo sido excluída doença intersticial renal com perda de potássio. Actualmente, seguida em consulta de Psiquiatria por provável síndrome de Munchausen, por suspeita de indução crónica de vómito. CONCLUSÃO Apresentamos este caso pela raridade da entidade clínica. São geralmente tumores não secretores e a maioria dos doentes estão assintomáticos na altura do diagnóstico, tal como no caso apresentado. O prognóstico dos doentes submetidos a ressecção completa do tumor é excelente.
- Ganglioneuroma of the Adrenal Gland - a case reportPublication . Monteiro, AM; Alves, M; Souto, S; Luís, D; Silva, AI; Marques, OIntroduction: The adrenal ganglioneuroma are rare, benign and well differentiated tumors that arise from neural crest tissue. Most patients with adrenal ganglioneuroma are asymptomatic, and most of these are non-secreting tumors. They are usually found incidentally on abdominal imaging study for another reason. Case: A 53-year-old female, with a history of hypertension diagnosed at age 30, dyslipidaemia, depressive disorder and hysterectomy for uterine prolapse. Medicated with spironolactone, potassium, atorvastatin, omeprazole, fluoxetine and lorazepam. History of repeat hospitalizations in the Internal Medicine Service for recurrent hypokalaemia. During the investigation of hypertension and hypokalaemia, a hypodense nodule in the left adrenal gland was detected on abdominal CT. She was referred to our service of Endocrinology due to suspected primary aldosteronism. She presented with asthenia, anorexia, cramps and muscle aches with a few months of evolution. Physical examination demonstrated no significant finding. Adrenal CT showed a left adrenal with hypodense nodule with 3 cm. Abdominal-pelvic MRI revealed a left adrenal with complex cystic mass with thick walls, where it identifies a mural nodule with 11×7 mm, questioning the possibility of tumor or pseudocyst cystic degeneration, and of considering their surgical excision. Endocrine tests were normal. Left adrenalectomy was performed by laparoscopy. The histological diagnosis was adrenal ganglioneuroma. Nephrology consultation for investigation of hypokalemia excluded renal interstitial disease with potassium loss. Currently, she attends Psychiatric consultation on suspicion Munchausen syndrome. Conclusion: We present this case due to the rarity of the clinical entity and the clinical presentation, which initially pointed us to another diagnosis. Ganglioneuromas are generally non-secreting tumors, and most patients are asymptomatic at diagnosis, as in the case presented. The prognosis of patients who underwent complete tumor resection is excellent.
- Gliosarcoma with neuroaxis metastases.Publication . Ramos, R; Morais, N; Silva, AI; Almeida, RGliosarcomas are rare tumours of the central nervous system, with a well-known capacity for metastasis. When they metastasise, the dissemination occurs more frequently via the haematogenous route to extraneural sites. Metastasis-spread through the cerebrospinal fluid is extremely rare. We present the case of a 58-year-old man who underwent a gross total resection of a lesion in the left temporal lobe. The histological findings revealed a gliosarcoma and the patient received radiotherapy followed by chemotherapy. Seven months after surgery, while the patient remained neurologically intact, brain and spinal cord MRI revealed tumour recurrence and neuroaxis metastases through the traffic routes of the cerebrospinal fluid. The patient died 8 months after the diagnosis. A PubMed search regarding metastatic gliosarcoma up to June 2015 was also carried out. To the best of our knowledge, this is the first case report of gliosarcoma metastases to the brain and spinal cord leptomeninges.
- Hemangioblastoma RenalPublication . Ferreira, M; Teixeira, M; Silva, AI; Pardal, F