Elizabeth Schneider Gugelmin

Increased Incidence of Choroid Plexus Carcinoma Due to the Germline TP53 R337H Mutation in Southern Brazil

Background Choroid plexus carcinomas (CPC) are rare tumors predominantly found in children. Given the high frequency of the germline R337H mutation in the TP53 gene in southern Brazil, we have evaluated the frequency of the R337H mutation in families with CPC in children. Methodology/Principal Findings The present series included 29 patients that were admitted to the same institution from 1992 to 2010, including 22 children with CPC (0.08–13.6 years of age at diagnosis) and 7 children with papilloma of the choroid plexus (Pp; 0.5–9.8 years of age). Surgical resection was possible in 28 children. Blood and/or tumor DNA was extracted and analyzed using PCR-RFLP and results were confirmed by sequencing 240 bp of the TP53 exon 10. The patients, all parents, and some relatives submitted samples for blood DNA analysis. In addition, we have also examined the presence of the mutation in DNA from paraffin-embedded tumor samples to evaluate loss of heterozygosity. We found 63.3% (14/22) of the CPC patients positive for the germline R337H mutation; CPC samples were either heterozygous (n = 7), lost only the wild-type (n = 4), or only the R337H copy (n = 2). One CPC sample was not available. All Pp cases (7/7, 100%) were negative for R337H. Cure (>5 years survival free of disease) was observed in 18.1% of the CPC cases with the R337H mutation (2/11), 71.4% of the Pp (5/7), and 25% of CPC cases negative for the R337H mutation (2/8). Family history of cancer (with 2 or more cancer cases) was exclusively identified on the parental side segregating the R337H mutation, and 50% (7/14) of them were compatible with Li-Fraumeni-like syndrome. Significance Our results show for the first time that the R337H TP53 mutation is responsible for 63% of the CPC cases in children, suggesting a higher incidence of CPC in southern Brazil.

Tumores de plexo coróide: estudo epidemiológico comparativo de 24 casos

Tumours derived from choroid plexus are rare central nervous system neoplasms affecting mainly children. This study presents a series of 38 patients with neuroectodermal tumours. Twenty four of them had the histological and/or immunohistochemical diagnosis of choroid plexus carcinoma (CPC). Sixteen of these patients were male. The left lateral ventricle was affected in most cases. Main clinical features were: hydrocephalus, intracranial hypertension and convulsion. All the patients were treated by surgery. There were 2 deaths due to surgical complications. Nine patients had recurrence, dying in a intermediate time of 12.3 months and 7 patients remain alive. The other cases did not present available data. CPC is very prevalent in Curitiba when compared to other choroid plexus tumours and it might be related to some pathogenic agent.

Meduloepitelioma teratóide maligno do globo ocular: relato de caso e revisão da literatura

Os autores relatam um caso de meduloepitelioma teratoide maligno intra-ocular acometendo uma menina de 7 anos com historia de glaucoma congenito. O padrao histologico demonstrou ilhas de epitelio primitivo, com frequentes estruturas tubulares e focos de cartilagem. Apos procedimento cirurgico, a paciente encontra-se bem, sem evidencia de recorrencia tumoral.

Immunohistochemical expression of sulfhydryl oxidase (QSOX1) in pediatric medulloblastomas

AbstractBackgroundMedulloblastoma is a malignant, invasive embryonal tumor of the cerebellum and accounts for 20% of intracranial tumors in children. QSOX1, whose functions include formation of disulphide bridges, which are needed for correct protein folding and stability, formation of the extracellular matrix, regulation of the redox status and cell cycle control, appears to be involved in apoptosis in pathological states such as cancer. Thus, the aim of this study was to investigate the immunohistochemical expression of QSOX1 in medulloblastomas and nonneoplastic cerebellum.MethodsHistology blocks of pediatric medulloblastomas were separated and two representative areas of the tumors and non-neoplastic cerebellum samples were used to construct tissue microarrays (TMAs) that were stained with an anti-QSOX1 antibody, and the slides were read using image analysis software.ResultsQSOX1 immunoexpression was observed in the non-neoplastic cerebellum samples and the medulloblastoma samples. There was no statistically significant relationship between QSOX1 immunopositivity in the medulloblastoma samples and the clinical and pathological variables.ConclusionsAlthough QSOX1 did not prove useful for stratifying patients into risk groups, tumor cells and the fibrillar extracellular matrix were positive for this marker, indicating that this enzyme may be involved in the pathogenesis of medulloblastoma.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1822040654139436

Immunohistochemical expression of p53, BCL-2, BAX and VEGFR1 proteins in nephroblastomas

INTRODUCAO: O nefroblastoma, ou tumor de Wilms, e a neoplasia renal mais frequente na infância. Embora o prognostico seja favoravel para a maioria dos pacientes, muitos evoluem para recidiva ou obito. A caracterizacao de grupos de risco por meio de marcadores imuno-histoquimicos tem por objetivo adequar o tratamento ao grupo de risco e reduzir recidivas e obitos. Entre os marcadores mais estudados estao p53, B-cell lymphoma 2 (BCL-2), BCL-2 associated protein X (BAX) e fator de crescimento vascular endotelial e seu receptor 1 (VEGFR1), relacionados com a via apoptotica, o reparo do acido desoxirribonucleico (DNA) e a neovascularizacao. OBJETIVO: O objetivo deste estudo e avaliar a expressao imuno-histoquimica de p53, BCL-2, BAX e VEGFR1 em amostras de nefroblastoma humano e correlaciona-las com fatores prognosticos clinico-patologicos. MATERIAL E METODO: Foram utilizadas 29 amostras de nefroblastomas retiradas dos Servicos de Anatomia Patologica de dois hospitais de Curitiba, com diagnosticos entre 1994 e 2007. Por meio da tecnica de imunoperoxidase, com as amostras em arranjo tecidual em matriz, realizou-se analise da imuno-histoquimica desses marcadores e sua comparacao com fatores prognosticos clinico-patologicos. RESULTADOS: A maior imunoexpressao de VEGFR1 nos componentes blastematoso e epitelial mostrou associacao positiva ao grupo de risco, sendo que isso poderia estar relacionado com a maior capacidade de invasao vascular neoplasica que pode ser conferida por esse fator de crescimento endotelial, aumentando, assim, as chances de metastases e alterando o estadimento, o grupo de risco e a evolucao clinica. CONCLUSAO: A expressao imuno-histoquimica aumentada de VEGFR1 mostrou associacao diretamente proporcional ao grupo de risco dos pacientes com nefroblastoma.