RESUMO
cAMP pathway activation by thyrotropin (TSH) induces differentiation and gene expression in thyrocytes. We investigated which partners of the cAMP cascade regulate gene expression modulations: protein kinase A and/or the exchange proteins directly activated by cAMP (Epac). Human primary cultured thyrocytes were analysed by microarrays after treatment with the adenylate cyclase activator forskolin, the protein kinase A (PKA) activator 6-MB-cAMP and the Epac-selective cAMP analog 8-pCPT-2'-O-Me-cAMP (007) alone or combined with 6-MB-cAMP. Profiles were compared to those of TSH. Cultures treated with the adenylate cyclase- or the PKA activator alone or the latter combined with 007 had profiles similar to those induced by TSH. mRNA profiles of 007-treated cultures were highly distinct from TSH-treated cells, suggesting that TSH-modulated gene expressions are mainly modulated by cAMP and PKA and not through Epac in cultured human thyroid cells. To investigate whether the Epac-Rap-RapGAP pathway could play a potential role in thyroid tumorigenesis, the mRNA expressions of its constituent proteins were investigated in two malignant thyroid tumor types. Modulations of this pathway suggest an increased Rap pathway activity in these cancers independent from cAMP activation.
Assuntos
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Glândula Tireoide/patologia , Tireotropina/fisiologia , Adenilil Ciclases/metabolismo , Bucladesina/análogos & derivados , Bucladesina/farmacologia , Carcinoma , Carcinoma Papilar , Células Cultivadas , Colforsina/farmacologia , AMP Cíclico/análogos & derivados , AMP Cíclico/farmacologia , Ativadores de Enzimas/farmacologia , Expressão Gênica , Perfilação da Expressão Gênica , Fatores de Troca do Nucleotídeo Guanina/agonistas , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Cultura Primária de Células , Transdução de Sinais , Câncer Papilífero da Tireoide , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide/metabolismo , Tireotropina/farmacologia , Proteínas rap1 de Ligação ao GTP/genética , Proteínas rap1 de Ligação ao GTP/metabolismoRESUMO
BACKGROUND/AIMS: Liver pathology induced by chemotherapy (steatosis or vascular injury) is known to increase the liver's sensitivity to ischemia/ reperfusion (I/R) injury, thereby increasing morbidity and mortality after liver resection. Our aim was to assess whether ischemic preconditioning (IP) reduces I/R injury to livers with chemotherapy-induced pathology. METHODS: We analyzed a series of livers from patients treated with chemotherapy for colorectal cancer who underwent IP (n=30) or not (n=31) before hepatectomy. All but one of the livers exhibited chemotherapy-induced steatosis and/ or peliosis before the I/R insult. RESULTS: Necrosis was less frequent (p=0.038) in livers with IP than in the others. IP had no influence on apoptosis as assessed by terminal transferase uridyl nick-end labeling (TUNEL) assay or caspase-3, -8 and -9 expression. IP induced a twofold increase in B-cell leukemia/ lymphoma 2 (Bcl-2; p<0.05), which was localized to hepatocytes of centrolobular and peliotic areas and colocalized with the autophagy protein beclin-1 in livers with IP, suggesting their coordinated role in autophagy. Increased expression of the phosphorylated Bcl-2 was observed in preconditioned livers and was associated with a decreased immunoprecipitation of beclin-1 and the increased expression of light chain 3 type II (LC3-II). The increased number of autophagic vacuoles seen by electron microscopy confirmed an association of autophagy in chemotherapy-injured livers following IP. However, the differences in protein expression were not reflected in postresection liver-injury tests or measure of patient morbidity. CONCLUSIONS: IP is associated with a reduction in necrosis of hepatocytes already damaged by chemotherapy and an activation of autophagy. Bcl-2 and beclin-1 could be major targets in the regulation of cell death during I/R injury.
Assuntos
Precondicionamento Isquêmico , Fígado/irrigação sanguínea , Fígado/patologia , Idoso , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Autofagia , Proteína Beclina-1 , Neoplasias Colorretais/tratamento farmacológico , Feminino , Humanos , Fígado/lesões , Fígado/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Necrose , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Traumatismo por Reperfusão/prevenção & controleRESUMO
BACKGROUND/AIMS: The aim of the present study was to identify the factors of recurrence for digestive endocrine tumours resected with curative intent. METHODOLOGY: 170 endocrine digestive tumours were reviewed from January 1997 to January 1997, Twenty eight patients were selected in this study. Localization of tumours were as follows: 14 duodenopancreatic (DP) and 14 Digestive (DT: 9 small bowel and 4 appendix). The following factors were investigated: primary site, hormonal clinical symptom, and differentiation. RESULTS: Twenty eight patients (12 men) were selected. Median age was 48 (range, 23-79) yrs. All resection of metastasis were performed during the same procedure of primary tumour resection. There were 14 DT and 14 non functional DP tumours. For 28 patients, the only factor of recurrence was endocrine pancreatic tumour (p = 0.02). For non functional DP, the rate of recurrence was significantly dependent on histology and the expression of ki67 antigen and presence of metastasis. Survival free of disease for DT were: 100%,80% at 1, 5 yrs, and for DP they were 93%, 50%, 33% at 1, 3, 5 yrs, respectively. CONCLUSION: The expression of the Ki67 antigen and differentiation seem to be good indicators for DP recurrence and may need an adjuvant treatment despite the R0 resection.
Assuntos
Neoplasias das Glândulas Endócrinas/cirurgia , Neoplasias Gastrointestinais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Neoplasias das Glândulas Endócrinas/mortalidade , Neoplasias das Glândulas Endócrinas/patologia , Feminino , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Estatísticas não ParamétricasRESUMO
Cell lines are crucial to elucidate mechanisms of tumorigenesis and serve as tools for cancer treatment screenings. Therefore, careful validation of whether these models have conserved properties of in vivo tumors is highly important. Thyrocyte-derived tumors are very interesting for cancer biology studies because from one cell type, at least five histologically characterized different benign and malignant tumor types can arise. To investigate whether thyroid tumor-derived cell lines are representative in vitro models, characteristics of eight of those cell lines were investigated with microarrays, differentiation markers, and karyotyping. Our results indicate that these cell lines derived from differentiated and undifferentiated tumor types have evolved in vitro into similar phenotypes with gene expression profiles the closest to in vivo undifferentiated tumors. Accordingly, the absence of expression of most thyrocyte-specific genes, the nonresponsiveness to thyrotropin, as well as their large number of chromosomal abnormalities, suggest that these cell lines have acquired characteristics of fully dedifferentiated cells. They represent the outcome of an adaptation and evolution in vitro, which questions the reliability of these cell lines as models for differentiated tumors. However, they may represent useful models for undifferentiated cancers, and by their comparison with differentiated cells, can help to define the genes involved in the differentiation/dedifferentiation process. The use of any cell line as a model for a cancer therefore requires prior careful and thorough validation for the investigated property.
Assuntos
Adenoma/patologia , Carcinoma Papilar/patologia , Diferenciação Celular , Linhagem Celular Tumoral , Neoplasias da Glândula Tireoide/patologia , Adenoma/genética , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Carcinoma Papilar/genética , Diferenciação Celular/genética , Análise por Conglomerados , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Cariotipagem , Análise de Sequência com Séries de Oligonucleotídeos , Especificidade de Órgãos/genética , Fenótipo , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/genética , Tireotropina/farmacologiaRESUMO
BACKGROUND: The identification of individuals who should undergo hereditary nonpolyposis colorectal cancer (HNPCC) genetic testing remains a critical issue. The Bethesda guidelines were developed to preselect patients for microsatellite instability (MSI) testing before germline mutation screening. These criteria have been revised, and a new set of recommendations, the revised Bethesda guidelines, has been proposed. OBJECTIVE: To evaluate the performance of these revised guidelines for identifying patients with HNPCC in a series of unselected consecutive patients and compare this revised guidelines-based approach with a molecular strategy (MSI testing for all tumors, followed by exclusion of MSI-positive sporadic cases from mutational testing). PATIENTS AND METHODS: The study included 214 patients with newly diagnosed colorectal cancer. The MSI analysis was performed for all tumors. Germline testing, guided by immunohistochemical staining for mismatch repair proteins, was performed for patients with MSI-positive tumors. Sporadic MSI-positive tumors were identified by screening for BRAF mutation and MLH1 promoter methylation. RESULTS: Ninety patients (42.1%) met the revised guidelines. Twenty-one patients (9.8%) had MSI-positive tumors. Germline testing identified eight mutations (3.7%) (MSH2 N = 5, MLH1 N = 2, MSH6 N =1). The revised guidelines failed to identify 2 of the 8 probands (aged 67 and 81 yr, both with no family history). In contrast, the molecular strategy identified all patients requiring testing for germline mutation. The percentages of patients selected for germline testing by the revised guidelines and the molecular strategy were 4.2% and 5.1%, respectively. CONCLUSIONS: The revised Bethesda guidelines did not identify all HNPCC cases in our series. The molecular approach identified all HNPCC patients with MSI-positive tumors, increasing the workload for germline testing only slightly.
Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Testes Genéticos , Guias de Prática Clínica como Assunto , HumanosRESUMO
We report a case of prosthetic hip infection due to Tropheryma whipplei in a 74-year-old man not previously known to have Whipple's disease. Diagnosis was based on systematic 16S rRNA gene amplification and sequencing of samples obtained during revision hip arthroplasty.
Assuntos
Bioprótese/efeitos adversos , Prótese de Quadril/efeitos adversos , Infecções Relacionadas à Prótese/diagnóstico , Tropheryma/isolamento & purificação , Doença de Whipple/diagnóstico , Idoso , Humanos , Masculino , Reação em Cadeia da Polimerase , Infecções Relacionadas à Prótese/microbiologia , Tropheryma/classificação , Tropheryma/genética , Doença de Whipple/microbiologiaRESUMO
Normal human thyroid follicular epithelial cells exhibit a very low proliferative rate which in vitro is dramatically increased by RAS oncogene activation, resulting in clones displaying a phenotype consistent with that of a ras-induced follicular adenoma in vivo. Eventual spontaneous cessation of growth of these clones is closely correlated with increasing expression of the tumour suppressor gene p16(INK4a), suggesting that p16 may limit clonal expansion in this tumour model. We therefore hypothesised that p16 expression would also increase in vivo in follicular adenomas, and further that escape from growth control in follicular cancers would be accompanied by loss of p16 expression. This was tested using tissue microarrays, representing multiple stages of thyroid tumourigenesis. Whereas the majority of normal thyroids showed no immunostaining, p16 protein was readily detectable in follicular adenomas. Unexpectedly, however, p16 expression was also observed in follicular and papillary carcinomas. Poorly differentiated (insular) carcinomas showed either very intense staining, or a complete loss of staining. We conclude that loss of p16 is not necessary for malignant transformation in thyroid follicular cells, but that it may form one of two or more events needed for progression to more aggressive forms of thyroid cancer.
Assuntos
Adenoma/metabolismo , Transformação Celular Neoplásica/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Proteínas de Ciclo Celular/metabolismo , Ciclina A/metabolismo , Células Epiteliais/metabolismo , Humanos , Imuno-Histoquímica/métodos , Componente 2 do Complexo de Manutenção de Minicromossomo , Proteínas Nucleares/metabolismoRESUMO
Overexpression of T-cadherin (T-cad) transcripts occurs in approximately 50% of human hepatocellular carcinomas (HCCs). To elucidate T-cad functions in HCC, we examined T-cad protein expression in normal and tumoral human livers and hepatoma cell lines and investigated its influence on invasive potential of HCC using RNA interference silencing of T-cad expression in Mahlavu cells. Whereas T-cad expression was restricted to endothelial cells (EC) from large blood vessels in normal livers, it was up-regulated in sinusoidal EC from 8/15 invasive HCCs. Importantly, in three of them (38%) T-cad was detected in tumor cells within regions in which E-cadherin expression was absent. Among six hepatoma cell lines, only Mahlavu expressed T-cad but not E-cadherin. T-cad exhibited a globally punctuate distribution in quiescent Mahlavu and additionally it concentrated at the leading edge of migrating cells. Matrigel invasion assay revealed that Mahlavu possess a high invasive potential that was significantly inhibited by T-cad silencing. Wound healing and random motility assays demonstrated that inhibition of T-cad expression in Mahlavu significantly reduced their motility. We propose that T-cad expression in tumor cells might occur by cadherin-switching during epithelial-mesenchymal transition and may represent an additional mechanism contributing to HCC metastasis.
Assuntos
Caderinas/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Fígado/fisiologia , Animais , Técnicas de Cultura de Células , Divisão Celular , Linhagem Celular Tumoral , Movimento Celular , Primers do DNA , Células Endoteliais/fisiologia , Fibroblastos/fisiologia , Hepatócitos/fisiologia , Humanos , Fígado/citologia , Invasividade Neoplásica , RNA Interferente Pequeno/genética , Coelhos , Transcrição Gênica , Transfecção , CicatrizaçãoRESUMO
The purpose of this study was to use the microarray technology to define expression profiles characteristic of thyroid autonomous adenomas and relate these findings to physiological mechanisms. Experiments were performed on a series of separated adenomas and their normal counterparts on Micromax cDNA microarrays covering 2400 genes (analysis I), and on a pool of adenomatous tissues and their corresponding normal counterparts using microarrays of 18,000 spots (analysis II). Results for genes present on the two arrays corroborated and several gene regulations previously determined by Northern blotting or microarrays in similar lesions were confirmed. Five overexpressed and 24 underexpressed genes were also confirmed by real-time RT-PCR in some of the samples used for microarray analysis, and in additional tumor specimens. Our results show: (1) a change in the cell populations of the tumor, with a marked decrease in lymphocytes and blood cells and an increase in endothelial cells. The latter increase would correspond to the establishment of a close relation between thyrocytes and endothelial cells and is related to increased N-cadherin expression. It explains the increased blood flow in the tumor; (2) a homogeneity of tumor samples correlating with their common physiopathological mechanism: the constitutive activation of the thyrotropin (TSH)/cAMP cascade; (3) a low proportion of regulated genes consistent with the concept of a minimal deviation tumor; (4) a higher expression of genes coding for specific functional proteins, consistent with the functional hyperactivity of the tumors; (5) an increase of phosphodiesterase gene expression which explains the relatively low cyclic AMP levels measured in these tumors; (6) an overexpression of antiapoptotic genes and underexpression of proapoptotic genes compatible with their low apoptosis rate; (7) an overexpression of N-cadherin and downregulation of caveolins, which casts doubt about the use of these expressions as markers for malignancy.
Assuntos
Adenoma/genética , Adenoma/fisiopatologia , Perfilação da Expressão Gênica , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/fisiopatologia , Adolescente , Adulto , Idoso , Western Blotting , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The oncogenic pathways in mitochondrial-rich thyroid carcinomas are not clearly understood. To investigate the possible implication of mitochondrial abundance in the genesis of thyroid tumors, we have explored the gene expression profile of six oncocytic carcinomas and six mitochondrial-rich papillary carcinomas using cDNA-microarray technology. A supervised approach allowed us to identify 83 genes differentially expressed in the two types of carcinoma. These genes were classified according to their ontologic profiles. Three genes, NOS3, alpha-actinin-2 and alpha-catenin, suspected of playing a role in tumor genesis, were explored by quantitative RT-PCR analysis and immunohistochemistry. Of the 59 genes overexpressed in papillary carcinomas, 51% were involved in cell communication. Of the 24 genes overexpressed in oncocytic carcinomas, 84% were involved in mitochondrial and cellular metabolism. Our results suggest that mitochondrial respiratory chain complexes III and IV play a significant role in the regulation of reactive oxygen species production by oncocytic tumors.
Assuntos
Carcinoma Papilar/genética , Carcinoma/genética , Perfilação da Expressão Gênica/métodos , Oncogenes , Transdução de Sinais/genética , Neoplasias da Glândula Tireoide/genética , Actinina/genética , Comunicação Celular/genética , Proteínas do Citoesqueleto/genética , Humanos , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo III , Reação em Cadeia da Polimerase Via Transcriptase Reversa , alfa CateninaRESUMO
Ischemia triggers an inflammatory response that precipitates cell death during reperfusion. Several studies have shown that tissues are protected by ischemic preconditioning (IP) consisting of 10 min of ischemia followed by 10 min of reperfusion just before ischemia. The molecular basis of this protective effect is poorly understood. We used cDNA arrays (20K) to compare global gene expression in liver biopsies from living human liver donors who underwent IP (n=7) or not (n=7) just before liver devascularization. Microarray data were analyzed using pairedt test with a type I error rate fixed at alpha = 2.5 10(6) (Bonferroni correction). We found that 60 genes were differentially expressed (36 over- and 24 underexpressed in preconditioning group). After IP, the most significantly overexpressed gene was IL-1Ra. This was confirmed by immunoblotting. Differentially expressed were genes involved in apoptosis (NOD2, ephrin-A1, and calpain) and in the carbohydrate metabolism. A significant increase in the amount of the anti-apoptotic protein Bcl-2 in preconditioned livers but no change in the cleavage of procaspase-3, -8, and -9 was observed. We also observed an increase in the amount in the inducible nitric oxide synthase. Therefore, the benefits of IP may be associated with the overproduction of IL-1Ra, Bcl-2, and NO countering the proinflammatory and proapoptotic effects generated during ischemia-reperfusion.
Assuntos
Regulação da Expressão Gênica , Precondicionamento Isquêmico , Fígado/patologia , Óxido Nítrico Sintase Tipo II/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Traumatismo por Reperfusão , Sialoglicoproteínas/metabolismo , Adulto , Apoptose , Biópsia , Western Blotting , Carboidratos/química , Caspase 3 , Caspase 8 , Caspase 9 , Caspases/metabolismo , DNA Complementar/metabolismo , Efrina-A1/metabolismo , Feminino , Humanos , Immunoblotting , Imuno-Histoquímica , Inflamação , Proteína Antagonista do Receptor de Interleucina 1 , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/metabolismo , Reperfusão , Fatores de TempoRESUMO
Nodular tumor-like squamous metaplasia with Hashimoto's thyroiditis is an exceptional, benign condition presenting diagnostic difficulties for the pathologist. The main differential diagnosis is a sclerosing mucoepidermoid carcinoma (SMC) with eosinophilia. One case arising in a 50-year-old Caucasian man is reported. Histologically, the nodule consisted of large nests of squamous cells surrounded by connective tissue in Hashimoto's thyroiditis. We present the different histological criteria, allowing us to eliminate an SMC and other neoplastic tumors of the thyroid. The etiology of this tumor-like lesion, which is still under debate, is discussed.
Assuntos
Carcinoma Mucoepidermoide/patologia , Eosinofilia/patologia , Doença de Hashimoto/patologia , Neoplasias de Células Escamosas/patologia , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Carcinoma Mucoepidermoide/complicações , Diagnóstico Diferencial , Eosinofilia/complicações , Doença de Hashimoto/complicações , Humanos , Imuno-Histoquímica , Masculino , Metaplasia , Pessoa de Meia-Idade , Neoplasias de Células Escamosas/complicações , Neoplasias da Glândula Tireoide/complicaçõesRESUMO
Thyroid oncocytic adenomas are a class of tumors characterized by the presence of abundant mitochondria. We performed a differential display RT-PCR analysis on two oncocytic adenomas and their paired controls. We then carried out a microarray analysis using the 460 selected, differentially expressed clones on four other oncocytomas and their paired controls. Thirty genes, 12 encoded by mitochondrial DNA and 18 nuclear-encoded, were overexpressed by a factor of at least 2 in the tumors compared with the controls. Seven of the 18 nuclear-encoded genes are involved in protein metabolism: DKFZP434I116, B3GTL, SNX19, RP42, SENP1, UBE2D3, and the CTSB gene, which is known to be particularly deregulated in most thyroid tumors. Other genes are implicated in signal transduction (ITGAV) or tumorigenesis (AF1q). Immunohistochemistry allowed us to confirm overexpression of the ITGAV and CTSB genes at the protein level and showed a marked relocation of the CTSB protein. We confirmed the overexpression of the AF1q oncogene in 56% of 18 oncocytic tumors by quantitative RT-PCR analysis, which attested to the heterogeneity of these tumors. Our results show an increased expression of genes involved in protein metabolism in oncocytoma, the significance of which requires investigation.
Assuntos
Adenoma/genética , Perfilação da Expressão Gênica , Neoplasias da Glândula Tireoide/genética , Translocador 2 do Nucleotídeo Adenina/genética , Adenoma/metabolismo , DNA Mitocondrial/genética , Humanos , Canais Iônicos , Proteínas de Membrana Transportadoras/genética , Proteínas Mitocondriais/genética , Proteínas de Neoplasias/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias da Glândula Tireoide/metabolismo , Proteína Desacopladora 2RESUMO
Oncocytomas are large cell tumors characterized by an abnormal proliferation of mitochondria. To investigate this phenomenon in thyroid oncocytomas, we determined gene expression profiles of 87 samples using microarrays of 6720 PCR products from cDNA clones. Samples included 29 thyroid oncocytomas and six papillary carcinomas, the remainder representing other thyroid pathologies or mitochondria-rich tumor samples, normal thyroid samples, and two thyroid cell lines. Hierarchical clustering and supervised analysis identified two specific oncocytic clusters and 163 distinctly regulated genes between oncocytoma and normal thyroid. Differential expression of five selected genes (APOD, BCL-2, COX, CTSB, and MAP2) was confirmed by immunohistochemistry. The two specific oncocytic clusters were rich in mitochondrial genes and revealed coordinated expression of nuclear and mitochondrial respiratory chain genes. We also observed the up-regulation of genes involved in mitochondrial biogenesis, such as nuclear respiratory factor 1 and the endothelial nitric oxide synthase. Several oxidative metabolism genes were overexpressed in oncocytomas, including those from the tricarboxylic acid cycle (MDH1) and cytosolic glycolysis (GAPD, ENO1, and GPI). On the contrary, the lactate dehydrogenase A gene, involved in anaerobic metabolism, was down-regulated. Our results suggest that, unlike a large number of solid tumors, thyroid oncocytomas produce energy through an aerobic pathway.
Assuntos
Adenoma Oxífilo/genética , Adenoma Oxífilo/metabolismo , Perfilação da Expressão Gênica , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Transcrição Gênica , Regulação para Cima/genética , Adulto , Idoso , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Família Multigênica , Análise de Sequência com Séries de OligonucleotídeosRESUMO
OBJECTIVE: The malignancy of thyroid oncocytic tumours, or oncocytomas, is higher than that of follicular tumours. The aim of this study was to investigate the role of thyroid-specific genes in oncocytic tumours and papillary carcinomas. DESIGN AND METHODS: We compared 29 oncocytic tumours with 12 papillary carcinomas. Real-time quantitative PCR was used to measure the expression of thyroid-specific differentiation markers (thyrotrophin-stimulation hormone receptor (TSHR), thyroglobulin (TG) and Na(+)/I(-) symporter (NIS)), transcription factors (thyroid transcription factor-1 (TTF-1) and paired box gene-8 (PAX8)) and nuclear receptors (peroxisome proliferator-activated receptor (PPARgamma1) and thyroid hormone receptor (TRbeta1)) involved in thyroid carcinogenesis. RESULTS: TSHR, TTF-1 and TRbeta1 levels were significantly lower in oncocytic tumours than in papillary carcinomas, as a result of specific biological changes in oncocytic tumours. However, PAX8 and PPARgamma1 did not seem to be involved in the process. Applying the criterion of the underexpression of the thyroid-specific differentiation markers, TSHR, TG and NIS, we classified the oncocytic tumours and papillary carcinomas into three groups. In the first, all three markers were underexpressed; in the second, TSHR was normal while TG and NIS were underexpressed; and in the third, only NIS was underexpressed. The expression patterns revealed that 13 of the 24 oncocytic adenomas underexpressing TSHR in our study, as did four of the five oncocytic carcinomas. CONCLUSION: Cases of oncocytic adenoma associated with low levels of TSHR could be putative oncocytic carcinomas and should therefore receive adequate follow-up [corrected].
Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Receptores da Tireotropina/biossíntese , Receptores da Tireotropina/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/metabolismo , Adenocarcinoma Folicular/patologia , Adenocarcinoma Papilar/genética , Adenocarcinoma Papilar/metabolismo , Adenocarcinoma Papilar/patologia , Adenoma/genética , Adenoma/metabolismo , Adenoma/patologia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fator de Transcrição PAX8 , Fatores de Transcrição Box Pareados , Reação em Cadeia da Polimerase , RNA Neoplásico/química , RNA Neoplásico/genética , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Simportadores/genética , Simportadores/metabolismo , Tireoglobulina/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Fator Nuclear 1 de Tireoide , Transativadores/genética , Transativadores/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
We evaluated the interobserver and intraobserver reproducibility in the histopathology of follicular thyroid carcinoma (FTC). Forty-one anonymous FTC pathology slides were independently reviewed by 5 pathologists, and 31 of them were also evaluated twice by the same pathologist. A final consensus diagnosis (FCD) was made at the end of the study. Interobserver and intraobserver agreement was determined as the kappa statistic for qualitative data and intraclass correlation coefficient for quantitative data. The agreement between the 5 observers' initial diagnosis and the FCD was 0.69, 0.41, 0.35, 0.28 and 0.11, respectively, strongly suggesting a leadership phenomenon. The FCD classified 30 cases as malignant, including 24 cases diagnosed as FTC. There was unanimous agreement about 13 of the 24 FTCs. Diagnostic reproducibility was found to be acceptable for the nonminimally invasive FTC. Diagnostic discrepancies occurred in 57% of the seven cases classified as minimally invasive FTC by the FCD. FCD excluded malignancy in 11 cases including 6 atypical adenomas. Interobserver and intraobserver agreement for FTC diagnosis was 0.23 (standard error [SE], 0.04) and 0.68, respectively. Interobserver and intraobserver agreement for the presence of vascular invasion was 0.20 (SE, 0.04) and 0.51, respectively, contrasting with a moderate to substantial level of agreement when considering the number of vascular invasion. Interobserver and intraobserver agreement for nucleus optical clearing were slight and moderate, respectively. The importance of the study is the confirmation that diagnostic reproducibility of minimally invasive FTC is low and that this has clinical implications, and also implications for the design of studies into the treatment and outcome of FTC.
Assuntos
Adenocarcinoma Folicular/patologia , Carcinoma Papilar, Variante Folicular/patologia , Variações Dependentes do Observador , Neoplasias da Glândula Tireoide/patologia , Humanos , Invasividade Neoplásica , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
OBJECTIVE: Thyroid surgery is common and complications are not rare. High-intensity focused ultrasound (HIFU) could be a possible minimally invasive alternative to surgery. The aim of this study was to assess the feasibility of using HIFU to obtain localized ablation of thyroid tissue without affecting neighboring structures. METHODS: The ewe was chosen as the model because its thyroid is easily accessible, with a size comparable to the human gland. An HIFU device designed to treat human prostate cancer was used. Eight ewes were anesthetised and their thyroids were ablated with ultrasound-guided HIFU. HIFU was generated by a 3-MHz spherical piezocomposite transducer that delivered an average of 24 (range, 9-44) ultrasound pulses per lobe covering a mean volume of 0.7 cm(3) (range, 0.2-1.8). RESULTS: Ewes were sacrificed 6-13 days after HIFU treatment and the anterior part of the neck was fixed in formalin before macroscopic and microscopic examinations. Adverse events occurred mainly for the first treated ewes before the energy delivered to the thyroid tissues was fully mastered: one animal died 3 days after HIFU, most probably because of inhalation pneumonia; the ultrasound beam hit adjacent organs in three animals. As expected, typical histologic lesions of the thyroid were obtained: central coagulative necrosis with ghost vesicular structures, disappearance of the nuclei, and cytoplasmic flocculation. At the periphery of the necrotic zone, a cell reaction was observed with fibroblastic granulation tissue, mononuclear cell infiltrate and regenerating thyroid tissue. CONCLUSION: The results of this preliminary study confirm the possibility of using HIFU in order to destroy a defined area in thyroid tissue. Future experiments in ewes will be focused on the safety of the method by refining the HIFU parameters and by developing a new equipment specially built for the thyroid.
Assuntos
Glândula Tireoide/cirurgia , Ultrassom , Anestesia , Animais , Estudos de Viabilidade , Feminino , Ovinos , Glândula Tireoide/anatomia & histologia , Glândula Tireoide/diagnóstico por imagem , Traqueia/lesões , Traqueia/patologia , Ultrassom/efeitos adversos , UltrassonografiaRESUMO
Endocervicosis of the urinary bladder is a rare non-neoplastic condition characterized by endocervical-type glands deeply situated in the urinary bladder wall of women of reproductive age. We compared the immunohistochemical phenotype of a case of endocervicosis in a 35-year-old woman with four normal uterine endocervices. We tested antibodies known as reactive in the uterus and not mentioned or negative in the urothelium (HBME-1, estrogen receptor (ER), progesterone receptors (PR), DF3, Chromogranin). The proliferative index was assessed with MIB-1 antibody. Endocervicosis glands displayed stronger expression of HBME-1, ER and PR than normal endocervices, while the urothelium was negative. There was no difference in DF3 expression. The number of Chromogranin-positive cells was higher in endocervicosis than in the endocervices. The proliferative index was higher in the endocervicosis glands (15%) than in the normal endocervices (mean 3%), but was within the normal range established for endocervical glands. Our results confirm the endocervical nature of endocervicosis and constitute further arguments for the mullerian origin hypothesis. The only modestly increased proliferative index, as compared to endocervical malignancies, is consistent with a benign diagnosis.
Assuntos
Colo do Útero/patologia , Coristoma/patologia , Doenças da Bexiga Urinária/patologia , Adulto , Biomarcadores/análise , Biomarcadores Tumorais/metabolismo , Divisão Celular , Colo do Útero/metabolismo , Coristoma/metabolismo , Cromograninas/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Células Estromais/citologia , Células Estromais/metabolismo , Doenças da Bexiga Urinária/metabolismoRESUMO
A thoracic aortic aneurysm was diagnosed in a 6-month-old male Leonberg dog by use of radiography, transthoracic and transesophageal echocardiography, and magnetic resonance imaging. The aneurysm was associated with a twisted ascending aorta and dilatation of several other thoracic arteries (pulmonary trunk, brachiocephalic trunk, and left subclavian artery). Histologic examination of the aorta revealed cystic medial necrosis, with disruption of the elastic network, collagen fibers, and the muscle glycoprotein fibrillin-1. The dam and sire of the dog and 8 littermates were examined by use of transthoracic echocardiography. The sire and 1 male littermate also had an aneurysm of the ascending aorta. To the authors' knowledge, this is the first report of familial aortic aneurysm in dogs.
Assuntos
Aneurisma Aórtico/veterinária , Animais , Aorta/anormalidades , Aorta/diagnóstico por imagem , Aorta/patologia , Aorta Torácica/patologia , Aneurisma Aórtico/diagnóstico , Aneurisma Aórtico/genética , Cruzamento , Diagnóstico Diferencial , Cães , Ecocardiografia Doppler em Cores/veterinária , Ecocardiografia Transesofagiana/veterinária , Imageamento por Ressonância Magnética/veterinária , Masculino , Artéria Subclávia/anormalidades , Artérias Torácicas/anormalidadesRESUMO
Pleomorphic carcinoma, firstly described in the lung, is exceptional in the digestive tract. This tumor is often associated with fever and peripheral blood leukocytosis. The histological feature is characterized by giant pleomorphic often multinucleated cells with dense neutrophil infiltration and frequent phagocytosis of neutrophils by the tumor cells. Expression of epithelial markers confirm the diagnosis. The prognosis is very poor. We hereby report one case of pleomorphic carcinoma unusually situated in the large intestine, emphasizing difficulties encountered in establishing diagnosis.