CDHI promoter hypermethylation and E-cadherin protein expression in infiltrating breast cancer

Background: the E-cadherin gene (CDH1) maps, at chromosome 16q22.1, a region often associated with loss of heterozygosity (LOH) in human breast cancer. LOH at this site is thought to lead to loss of function of this tumor suppressor gene and was correlated with decreased disease-free survival, poor prognosis, and metastasis. Differential CpG island methylation in the promoter region of the CDH1 gene might be an alternative way for the loss of expression and function of E-cadherin, leading to loss of tissue integrity, an essential step in tumor progression.Methods: the aim of our study was to assess, by Methylation-Specific Polymerase Chain Reaction (MSP), the methylation pattern of the CDH1 gene and its possible correlation with the expression of E-cadherin and other standard immunohistochemical parameters (Her-2, ER, PgR, p53, and K-67) in a series of 79 primary breast cancers ( 71 infiltrating ductal, 5 infiltrating lobular, 1 metaplastic, 1 apocrine, and 1 papillary carcinoma).Results: CDH1 hypermethylation was observed in 72% of the cases including 52/71 ductal, 4/5 lobular carcinomas and 1 apocrine carcinoma. Reduced levels of E-cadherin protein were observed in 85% of our samples. Although not statistically significant, the levels of E-cadherin expression tended to diminish with the CDH1 promoter region methylation. In the group of 71 ductal cancinomas, most of the cases of showing CDH1 hypermethylation also presented reduced levels of expression of ER and PgR proteins, and a possible association was observed between CDH1 methylation and ER expression ( p = 0.0301, Fisher's exact test). However, this finding was not considered significant after Bonferroni correction of p-value.Conclusion: Our preliminary findings suggested that abnormal CDH1 methylation occurs in high frequencies in infiltrating breast cancers associated with a decrease in E-cadherin expression in a subgroup of cases characterized by loss of expression of other important genes to the mammary carcinogenesis process, probably due to the disruption of the mechanism of maintenance of DNA methylation in tumoral cells.

Recrudescence of Toxoplasma gondii infection in chronically infected rats (Rattus norvegicus)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Squamous cell carcinoma in vaginal fundus in a Brahman cow

É descrito o carcinoma de células escamosas (CCE) no fundo vaginal de uma vaca. O diagnóstico de CCE moderadamente diferenciado foi confirmado através do exame histopatológico. Os testes imunoistoquímicos com os marcadores p53 e Ki67 realizados em amostras do tumor confirmaram a mutação na p53 e aumento da proliferação celular.

Patterns of nucleolar activity during spermatogenesis of two triatomines, Panstrongylus megistus and P-herreri

The present work analyzed spermatogenesis in two species of triatomines (genus Panstrongylus) using silver-ion impregnation. The sex chromosomes of P. megistus and P. herreri had nucleolar organizing activity and became strongly impregnated during the phases of meiotic prophase I. Fragmentation of the nucleolus occurred in both species during the meiotic cycle. The nucleolar region could be observed up to diakinesis in meiotic prophase after which only nucleolar bodies and fragments were seen. Postmeiotic reactivation of rRNA synthesis occurred in these two species and was probably related to cell differentiation.

Epigenetic Silencing of CRABP2 and MX1 in Head and Neck Tumors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Gene Mutations and Polymorphisms of TP53 and FHIT in Chronic Esophagitis and Esophageal Carcinoma

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Study of the nucleolar cycle and ribosomal RNA distribution during meiosis in triatomines (Triatominae, Heteroptera)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Alterations of the TP53 Gene in Gastric and Esophageal Carcinogenesis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Esterase inhibition in tadpoles of Scinax fuscovarius (Anura, Hylidae) as a biomarker for exposure to organophosphate pesticides

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influência da terapêutica hormonal prévia sobre os indicadores de prognóstico do câncer de mama em mulheres na pós-menopausa

OBJETIVO: avaliar a influência da terapêutica hormonal (TH) prévia sobre alguns indicadores de prognóstico do câncer de mama, em pacientes na pós-menopausa. MÉTODOS: estudo transversal por meio da aplicação de questionários e levantamento de prontuários. Foram entrevistadas 157 pacientes com diagnóstico de câncer de mama na pós-menopausa, registrando-se dados clínicos, antecedentes pessoais e familiares, uso de TH e mamografias. Nos prontuários foram obtidas informações sobre o câncer de mama quanto ao diâmetro do tumor, tipo de cirurgia e estudo imuno-histoquímico. Para a estatística empregou-se ANOVA e teste do chi2. RESULTADOS: 38,2% das pacientes eram ex-usuárias de TH e 61,8% não usuárias. O tempo médio de uso da TH foi de 3,7±3,6 anos. As ex-usuárias eram de menor faixa etária e com menor tempo de menopausa quando comparadas às não usuárias (p<0,05). Constatou-se que 26,8% das pacientes apresentavam antecedentes familiares de câncer de mama, em ambos os grupos. Entre as ex-usuárias de TH, 43,3% foram submetidas a mamografias prévias, ao passo que entre as não usuárias, apenas 11,3% (p<0,001). O diâmetro médio do tumor foi menor entre as ex-usuárias de TH (2,3±1,1 cm), com predomínio de quadrantectomias (60%), quando comparadas as não usuárias (3,3±1,5 cm e 32%, respectivamente) (p<0,001). No estudo imuno-histoquímico, observou-se correlação positiva entre a presença de receptores de estrogênio e progesterona positivos e o uso de TH (p<0,001). Não houve correlação entre TH e c-erbB-2 e p53. CONCLUSÃO: nesta casuística, as mulheres na pós-menopausa que usaram TH prévia ao diagnóstico de câncer de mama apresentaram indicadores de prognóstico mais favoráveis quando comparadas às não usuárias.

Paracoccidioidomycosis associated with acquired immunodificiency syndrome: report of seven cases

São apresentadas as características clínicas e evolutivas de sete pacientes (cinco masculinos e dois do sexo feminino), a maioria dos quais usuários de drogas ilícitas endovenosa, com paracoccidioidomicose associada à Síndrome da Imunodeficiência Adquirida (SIDA/AIDS). em quatro pacientes a paracoccidioidomicose comprometia os pulmões isoladamente, nos demais a doença era generalizada com envolvimento cutâneo. Apenas dois pacientes eram procedentes recentes da zona rural. O que nos faz presumir que nos demais a paracoccidioidomicose doença resultou da reativação de focos latentes da infecção. Dado o papel da imunidade medida por células na defesa do hospedeiro contra o Paracoccidioides brasiliensis, é de se prever crescente ocorrência da associação paracoccidioidomicose -SIDA/AIDS nas áreas endêmicas para ambas as enfermidades.

Aneuploidies, deletion, and overexpression of TP53 gene in intestinal metaplasia of patients without gastric cancer

Gastric carcinogenesis is attributable to interacting environmental and genetic factors, through a sequence of events including intestinal metaplasia. Using a fluorescence in situ hybridization technique, we investigated the occurrence of ancuploidies of chromosomes 3, 7, 8, 9, and 17, TP53 gene deletion, and expression of p53 in 21 intestinal metaplasia (IM) samples from cancer-free patients and in 20 gastric adenocarcinoma samples. Aneuploidies were found in 71% (15/21) of the IM samples. Trisomy of chromosomes 7 and 9 occurred mainly in complete-type IM; in the incomplete type, trisomy of chromosomes 7 and 8 were more commonly found. The TP53 gene deletion was observed in 60% (3/5) of the IM cases, and immunohistochemistry revealed p53 overexpression in 12% (2/17) of the analyzed IM cases. All gastric adenocarcinoma cases presented higher frequencies of trisomy or tetrasomy of chromosomes 3, 7, 8, 9, and 17. The TP53 deletion was found in all three of the gastric adenocarcinoma analyzed for it, and immunohistochemistry detected overexpression of protein p53 in 80% (12/15) of the analyzed cases. Our study revealed for the first time the presence of aneuploidies of chromosomes 7, 8, 9, and 17 and of TP53 gene deletion and overexpression in IM samples from cancer-free patients. These results suggest that IM and gastric adenocarcinoma may share the same genetic alterations. (C) 2004 Elsevier B.V. All rights reserved.

Consolidation and break-up of the South American platform in southeastern Brazil: Tectonothermal and denudation histories

The different tectonic stages that occurred at the end of the Proterozoic and during the Phanerozoic have an important bearing on the tectonothermal history of the South American Platform and its consolidation. Geochronological data (U/Pb monazite, Ar-40/Ar-39 whole rock) and apatite fission-track analysis, from Precambrian rocks of the southeastern Brazilian coastline, permit the modeling of a long-term thermal history of the crust and constrain variable denudation rates.Using these data, a temperature-time diagram reflects a period of accelerated exhumation during the end of the Brasiliano Orogeny, followed by long stability and reactivation of the platform during the Rifting Phase of the South Atlantic Ocean.U/Pb zircon and monazite (blocking temperature of ca. 650degreesC) data from a series of igneous bodies suggest that a tangential and transpressional tectonic regime occurred between 625 and 610 Ma. During the following escape tectonics, between 610 and 590 Ma the exhumation process indicates cooling rates of ca. 12degreesC/Ma. Ar-40/Ar-39 biotite ages between 540 and 510 Ma (ca. 300degreesC) and a corrected fission-track age on apatites (100degreesC) of 480 Ma indicate an exhumation event related to block tectonics with huge vertical displacement along shear zones.A long stabilization phase, with low exhumation, and cooling rate around 0.25degreesC/Ma was recorded from the Cambro/Ordovician to the Mesozoic. At 65 Ma an acceleration of the exhumation through denudation and reworking of the South American surface with cooling rate of 1.5degreesC/Ma is observed.The uplift of the Mantiqueira and Serra do Mar mountain ranges along the southeast Brazilian coastline works as a climatic barrier provoking lateral erosional processes causing long-term scarp retreat, combined with intense, but progressive denudation towards the continent. A denudation of 2.5 to 4 km was calculated for such processes. This lateral retreat of escarpments and flexural response can provide important insights regarding marginal isostatic uplift and the evolution of offshore sedimentary basins of southeast Brazil.

Characterizing subpopulations of neoplastic cells in serous effusions - the role of immunocytochemistry

OBJECTIVE: To analyze the role of immunochemistry in serous effusions.STUDY DESIGN: We analyzed cell blocks of 18 pleural and 18 peritoneal effusions diagnosed as malignant (18), benign (14) and suspicious (4). They were immunostained by the avidin-biotin complex method with a panel of four monoclonal antibodies-CEA, Ber-EP4, LeuM1 (CD15) and r53-and for lectins (Ulex europaeus) UEA-1, ConA and ConBr. RESULTS: Seventeen of the 18 cases of adenocarcinoma were positive for CEA (95%), 12 (66.6%)for Bev-EP4, 11 (61 %)for CD15 nild 11 (62 %)for p53. Twelve of the 18 (66.6%) were positive for UEA-1, CEA, Ber-EP4 and CD15. UEA-1 did not react with mesothelial cells. p53 Gave a positive reaction in only one case, reactive mesothelial cells. ConA and ConBr reacted indiscriminately with benign and malignant cells; thus, it was not useful in distinguishing between these cells.CONCLUSION: In this context no antibody used alone is reliable for corroborating a diagnosis, but the selective use of a small panel of three markers (CEA, Ber-EP4 and LeuM1) can be very useful in solving diagnostic difficulties in the cytodiagnosis of serous effusions.

Thermotectonic and fault dynamic analysis of Precambrian basement and tectonic constraints with the Parana basin

The Precambrian crystalline basement of southeast Brazil is affected by many Phanerozoic reactivations of shear zones that developed during the end of the Neoproterozoic in the Brasiliano orogeny. These reactivations with specific tectonic events, a multidisciplinary study was done, involving geology, paleostress, and structural analysis of faults, associated with apatite fission track methods along the northeastern border of the Parana basin in southeast Brazil.The results show that the study area consists of three main tectonic domains, which record different episodes of uplift and reactivation of faults. These faults were brittle in character and resulted in multiple generations of fault products as pseudotachylytes and ultracataclasites, foliated cataclasites and fault gouges.Based on geological evidence and fission track data, an uplift of basement rocks and related tectonic subsidence with consequent deposition in the Parana basin were modeled.The reactivations of the basement record successive uplift events during the Phanerozoic dated via corrected fission track ages, at 387 +/- 50 Ma (Ordovician); 193 +/- 19 Ma (Triassic); 142 +/- 18 Ma (Jurassic), 126 +/- 11 Ma (Early Cretaceous); 89 +/- 10 Ma (Late Cretaceous) and 69 +/- 10 Ma (Late Cretaceous). These results indicate differential uplift of tectonic domains of basement units, probably related to Parana basin subsidence. Six major sedimentary units (supersequences) that have been deposited with their bounding unconformities, seem to have a close relationship with the orogenic events during the evolution of southwestern Gondwana. (c) 2005 Elsevier Ltd. All rights reserved.