NDRG1 protein overexpression in malignant thyroid neoplasms

OBJECTIVES: The aim of this study was to examine the expression of the N-myc downstream-regulated gene 1 protein in benign and malignant lesions of the thyroid gland by immunohistochemistry. INTRODUCTION: N-myc downstream-regulated gene 1 encodes a protein whose expression is induced by various stimuli, including cell differentiation, exposure to heavy metals, hypoxia, and DNA damage. Increased N-myc downstream-regulated gene 1 expression has been detected in various types of tumors, but the role of N-myc downstream-regulated gene 1 expression in thyroid lesions remains to be determined. METHODS: A tissue microarray paraffin block containing 265 tissue fragments corresponding to normal thyroid, nodular goiter, follicular adenoma, papillary thyroid carcinoma (classical pattern and follicular variant), follicular carcinoma, and metastases of papillary and follicular thyroid carcinomas were analyzed by immunohistochemistry using a polyclonal anti- N-myc downstream-regulated gene 1 antibody. RESULTS: The immunohistochemical expression of N-myc downstream-regulated gene 1 was higher in carcinomas compared to normal thyroid glands and nodular goiters, with higher expression in classical papillary thyroid carcinomas and metastases of thyroid carcinomas (P < 0.001). A combined analysis showed higher immunohistochemical expression of NDRG1 in malignant lesions (classical pattern and follicular variant of papillary thyroid carcinomas, follicular carcinomas, and metastases of thyroid carcinomas) compared to benign thyroid lesions (goiter and follicular adenomas) (P = 0.043). In thyroid carcinomas, N-myc downstream-regulated gene 1 expression was significantly correlated with a more advanced TNM stage (P = 0.007) and age, metastasis, tumor extent, and size (AMES) high-risk group (P = 0.012). CONCLUSIONS: Thyroid carcinomas showed increased immunohistochemical N-myc downstream-regulated gene 1 expression compared to normal and benign thyroid lesions and is correlated with more advanced tumor stages.

Hiperparatireoidismo secundário: fatores prognósticos de recidiva atribuída ao implante após paratireoidectomia total e auto-implante / Secondary hyperparathyroidism: prognostic factors of graft-dependent recurrence after total parathyroidectomy adn parathyroid autotransplantation

Introdução: Quando o tratamento clínico do hiperparatireoidismo secundário falha, é recomendada a paratireoidectomia. Na DCCP HCFMUSP, a cirurgia de escolha é a paratireoidectomia total com auto-implante imediato de fragmentos de paratireoide em membro superior. Nestes casos, caso haja recidiva do hiperparatireoidismo, pode ser causada pelo tecido implantado e, em alguns casos, há necessidade de ressecção dos implantes. Objetivo: O estudo atual tem como objetivo avaliar os pacientes submetidos a este tratamento e identificar fatores clínicos que podem prever recidiva atribuída ao implante. Método: Analisamos retrospectivamente dados de 57 doentes e identificamos nove recidivas do hiperparatireoidismo atribuídas ao implante, que foram submetidos a 14 procedimentos de retirada. Escolhemos um grupo controle (pareado por sexo e idade) de pacientes submetidos a paratireoidectomia total com auto-implante, sem recidiva por pelo menos dois anos. Resultados: Analisamos dados clínicos e laboratoriais, assim como pesos e padrões histológicos das paratireoides operadas. Houve diferença estatisticamente significante entre a dosagem pré-operatória de PTH (p=0,0091), tamanho da paratireoide ressecada durante a primeira cirurgia (p=0,0052) e padrão nodular na paratireoide selecionada para implante (p=0,0152) e recidiva no implante. Oito dos nove pacientes diagnosticados com recidiva tiveram controle da doença após os procedimentos. Todos os dados estatisticamente significativos foram pré ou peri-operatórios, e podem ajudar em decisões intra-operatórias. Conclusões: Baseado no estudo, sugerimos que a quantidade de tecido paratireoideo necessário a ser implantado pode variar conforme a dosagem sérica de PTH, o tamanho das glândulas e a presença de hiperplasia nodular no intra-operatório. As glândulas maiores e com hiperplasia nodular devem ser evitadas para implante.

Introduction: When clinical treatment of secondary hyperparathyroidism fails, parathyroidectomy is mandatory. Total parathyroidectomy and immediate parathyroid autotransplantation in the forearm is the standard treatment at the DCCP HCFMUSP. In these cases, if hyperparathyroidism reccurs, it may be caused by hyperplastic graft tissue and, sometimes, reintervention is needed to resect hyperplasic implants. Objective: The present study seeks to evaluate patients submitted to this treatment and try to clarify clinical factors that could predict hyperparathyroidism recurrence due to graft hyperplasia. Method: We could retrospectively analyse data from 57 patients, and identify nine recurrences of hyperparathyroidism caused by graft hyperplasia, submitted to 14 implant resections. We choose a control group: autotransplantation without recurrence for at least two years (matched by age and sex). Results: We analyzed pre-operative clinical and laboratorial data, parathyroid weight and histological patterns. There were statistically significant differences among preoperative serum PTH (p=0,0091), parathyroid gland size resected during first surgery (p=0,0052) and nodular pattern at parathyroid chosen for transplantation (p=0,0152) and recurrence caused by graft tissue. In all patients, but one, the disease is controlled. All statistically significant identified risk factors were pre or perioperative and may help intra operative decisions. Conclusion: Based on this study, we suggest that the amount of graft tissue may be influenced by pre-op PTH levels, size of glands and presence of nodular hyperplasia. A large and/or nodular glands should be avoided for implants.

Avaliação do papel diagnóstico e prognóstico da expressão imunoistoquímica de NDRG1, osteonectina, VEGF-A, VEGF-C, Flk-1/KDR, HIF-1 e galectina-3 em espécimes tireoideanos por tissue microarrays / Study of the diagnostic and prognostic role of immunohistochemical expression of NDRG1, osteonectin, VEGF-A, VEGF-C, Flk-1/KDR, HIF-1 and galectin-3 in thyroid specimens by tissue microarray

INTRODUÇÃO: O crescimento e a progressão de diversos tipos de tumores dependem da angiogênese, isto é, a formação de novos vasos sanguíneos. Fatores da família do VEGF (VEGF-A, VEGF-C, Flk-1/KDR) são potentes mediadores da angiogênese e níveis elevados destes fatores podem ser detectados em vários tumores humanos. Outras proteínas como NDRG1, osteonectina, HIF-1 e galectina-3 encontram-se associadas, de modo indireto, à angiogênese. MÉTODOS: O objetivo deste estudo foi analisar a expressão imunoistoquímica de NDRG1, osteonectina, VEGF-A, VEGF-C, Flk-1/KDR, HIF-1 e galectina-3 em 265 lesões benignas e malignas da tireóide por tissue microarray (TMA), incluindo tireóide normal, bócio, adenoma folicular, carcinoma papilífero, carcinoma folicular e metástases de carcinoma papilífero e folicular da tireóide. Lâminas em diferentes níveis do bloco de TMA foram submetidas à reação imunoistoquímica utilizando-se anticorpos específicos contra NDRG1, osteonectina, VEGF-A, VEGF-C, Flk-1/KDR, HIF-1, galectina-3. Foi realizada uma avaliação semiquantitativa da expressão destas proteínas, analisando-se a intensidade de coloração e a porcentagem de células positivas para cada marcador. RESULTADOS: De um modo geral, a expressão de NDRG1, osteonectina, VEGF-A, VEGF-C, Flk-1/KDR, HIF-1 e galectina-3 foi maior nos carcinomas de tireóide em relação ao bócio e adenoma folicular. Dentre as proteínas estudadas, a galectina-3 foi aquela que apresentou melhor acurácia diagnóstica na distinção entre lesões benignas e malignas da tireóide, com uma sensibilidade 64,1% e especificidade de 94,4%. Nos carcinomas de tireóide, a expressão de NDRG1, VEGF-A, VEGF-C e HIF-1 apresentou correlação estatística significativa com estádio TNM mais avançado e alto risco pelo método AMES. A análise multivariada revelou que a idade 45 anos, o tamanho tumoral maior do que 4,0 cm, o estádio IV do TNM e a perda de expressão de galectina-3 foram fatores que contribuíram para a recorrência...

INTRODUCTION: The growth and progression of different types of tumors depend on angiogenesis, i.e., the formation of new blood vessels. Members of the VEGF family (VEGF-A, VEGF-C, Flk-1/KDR) are potent mediators of angiogenesis and elevated levels of these factors can be detected in various human tumors. Other proteins such as NDRG1, osteonectin, HIF-1 and galectin-3 are indirectly associated with angiogenesis. METHODS: The objective of this study was to investigate the immunohistochemical expression of NDRG1, osteonectin, VEGF-A, VEGF-C, Flk-1/KDR, HIF-1 and galectin-3 in 265 benign and malignant thyroid lesions by tissue microarray (TMA), including normal thyroid, goiter, follicular adenoma, papillary carcinoma, follicular carcinoma, and papillary and follicular thyroid carcinoma metastases. Slides obtained from different levels of the TMA block were submitted to immunohistochemistry using specific antibodies against NDRG1, osteonectin, VEGF-A, VEGF-C, Flk-1/KDR, HIF-1, and galectin-3. The expression of these proteins was analyzed semiquantitatively, evaluating the intensity of staining and the percentage of positive cells for each marker. RESULTS: In general, the expression of NDRG1, osteonectin, VEGF-A, VEGF-C, Flk-1/KDR, HIF-1 and galectin-3 was higher in thyroid carcinomas when compared to goiter and follicular adenoma. Among the proteins studied, galectin-3 presented the best diagnostic accuracy in the distinction between benign and malignant thyroid lesions, with a sensitivity of 64.1% and specificity of 94.4%. In thyroid carcinomas, the expression of NDRG1, VEGF-A, VEGF-C and HIF-1 was significantly correlated with a more advanced TNM stage and AMES high risk. Multivariate analysis revealed that age 45 years, tumor size > 4.0 cm, TNM stage IV and loss of expression of galectin-3 were associated with recurrence or death in patients with thyroid carcinoma. CONCLUSIONS: In thyroid carcinomas, the expression of NDRG1, VEGF-A, VEGF-C and HIF-1...

Salivary gland tumors in a Brazilian population: a retrospective study of 124 cases

Salivary gland tumors constitute a highly heterogeneous histopathologic group. There are few epidemiological studies of large series of benign and malignant salivary gland tumors in Brazil. MATERIAL AND METHODS: Hospital records of 124 patients with salivary gland tumors diagnosed from January 1993 to December 1999 were reviewed. The patients were analyzed according to gender, age, size, location, and histopathology of the tumor. RESULTS AND CONCLUSIONS: Patients with benign and malignant tumors presented with a mean age of 47.7 and 48.8 years, respectively. The frequency of benign tumors was 80 percent (n = 99) and malignant tumors 20 percent (n = 25). Tumors were localized in the parotid gland 71 percent (n = 88), in the submandibular gland 24 percent (n = 30), and in the minor salivary glands 5 percent (n = 6). The most common benign tumors were pleomorphic adenoma in 84 percent (n = 84) and Warthin's tumor in 13 percent (n = 13). Among malignant tumors, mucoepidermoid carcinoma was the most common in 52 percent (n = 13), adenoid cystic carcinoma occurred in 20 percent (n = 5), and carcinoma ex pleomorphic adenoma was detected in 12 percent (n = 3)

Histomorphometrical study of the elastic fiber system in the anterior cerebral artery of man

The aim of the present study was to quantify the distribution of the elastic fiber system within the wall of the anterior cerebral artery. The study is based on the works of Glynn (1940) and Stehbens (1989) concerning the incidence and origin of brain aneurysms and recent studies of the elastic fibers. The anterior cerebral artery was divided into three segments, S1, S2 and S3: S1 corresponds to the origin of the anterior cerebral artery, S2 is located at the junction of the anterior cerebral artery with the anterior communicating artery, and S3 at the junction of the rostrum and genu of the corpus callosum,which were submitted to routine histological procedures. A histomorphometrical study was undertaken using an estimation of the linear density (Ld) of the components of the fibrous elastic system which evaluates their full length in each segment. Data were analyzed using first order linear regression methods. The results show a decreasing quantity of elastic fibers in the three segments (S1>S2>S3). Study of the elastic fiber system may originate new concepts regarding the genesis of cerebral artery aneurysm