Augusta Mendes da Silva

Expression, mutation and copy number analysis of platelet-derived growth factor receptor A (PDGFRA) and its ligand PDGFA in gliomas

Background: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.

Impact of EGFR Genetic Variants on Glioma Risk and Patient Outcome

Background: The epidermal growth factor receptor (EGFR) regulates important cellular processes and is frequently implicated in human tumors. Three EGFR polymorphisms have been described as having a transcriptional regulatory function: two single-nucleotide polymorphisms in the essential promoter region, −216G/T and −191C/A, and a polymorphic (CA)n microsatellite sequence in intron 1. We aimed to elucidate the roles of these EGFR polymorphisms in glioma susceptibility and prognosis. Methods: We conducted a case–control study with 196 patients with glioma and 168 cancer-free controls. Unconditional multivariate logistic regression models were used to calculate ORs and 95% confidence intervals. A Cox regression model was used to evaluate associations with patient survival. False-positive report probabilities were also assessed. Results: None of the EGFR −216G/T variants was significantly associated with glioma risk. The −191C/A genotype was associated with higher risk for glioma when the (CA)n alleles were classified as short for ≤16 or ≤17 repeats. Independently of the (CA)n repeat cutoff point used, shorter (CA)n repeat variants were significantly associated with increased risk for glioma, particularly glioblastoma and oligodendroglioma. In all tested models with different (CA)n cutoff points, only −191C/A genotype was consistently associated with improved survival of patients with glioblastoma. Conclusions: Our findings implicate EGFR −191C/A and the (CA)n repeat polymorphisms as risk factors for gliomas, and suggest −191C/A as a prognostic marker in glioblastoma. Impact: Our data support a role of these EGFR polymorphisms in determining glioma susceptibility, with potential relevance for molecularly based stratification of patients with glioblastoma for individualized therapies. Cancer Epidemiol Biomarkers Prev; 20(12); 2610–7. ©2011 AACR.

Primary intimal sarcoma of the left atrium presenting with constitutional symptoms

Abstract Intimal (spindle-cell) sarcomas are exceptionally rare and are highly aggressive cardiac tumors. The authors describe a case of a 43-year-old female, presenting with a 3-month history of constitutional symptoms with fever, night sweats, anorexia and weight loss, associated with productive cough and pleural effusion that was admitted with clinical suspicion of pulmonary tuberculosis. The patient developed sudden acute heart failure symptoms during hospitalization, leading to mechanical ventilation. Computed tomography scan with contrast showed a cardiac tumor filling the left atrium causing compression of pulmonary veins. Surgical resection was performed and histologic examination revealed an intimal sarcoma. Although commenced on adjuvant chemotherapy, local tumor recurrence occurred with pericardium invasion. The patient died within 4 months of initial diagnosis. This report aims to describe an unusual presentation of this rare disease entity, and to discuss its highly aggressive clinical course.

An Itchy Problem: A Clinical Case of Crusted Scabies

Scabies is an infestation of the skin by the mite Sarcoptes scabiei. A more severe form called crusted or Norwegian scabies may occur in immunosuppressed patients and the elderly. Crusted scabies mostly differs from normal scabies by the exuberance of its lesions, body distribution and high contagiousness, and requires different and more prolonged treatment. Early recognition of the lesions and isolation precautions are crucial for disease control and prevention of transmission. The authors describe a clinical case of crusted scabies with pruritus and exuberant cutaneous lesions. LEARNING POINTS Crusted scabies is an infestation of the skin by the mite Sarcoptes scabiei that is highly contagious and results in an intensely pruritic eruption with exuberant cutaneous lesions. Crusted scabies occurs in patients with AIDS, lymphoma or compromised cellular immunity, and sometimes in older patients. It is characterized by an elevated burden of mites and does not have a characteristic distribution pattern. This disease requires strict isolation measures and treatment which differs from and is more prolonged than for scabies.

Subserous Eosinophilic Gastroenteritis: A Rare Cause of Ascites

Eosinophilic gastroenteritis is an inflammatory gastrointestinal disease characterized by eosinophilic infiltration of the digestive tract. The subserous type is the rarest form and diagnosis is challenging because the symptoms are heterogeneous and endoscopy may be non-diagnostic. The authors describe the clinical case of a 41-year-old female patient who was diagnosed with subserous eosinophilic gastroenteritis. This case highlights the importance of clinical suspicion of eosinophilic gastroenteritis in patients in the third to fifth decades of life with gastrointestinal symptoms, ascites and eosinophilia. LEARNING POINTS Subserous eosinophilic gastroenteritis is an uncommon inflammatory gastrointestinal disease with a challenging diagnosis because the symptoms are heterogeneous and endoscopy may be non-diagnostic. The diagnosis should be suspected in the presence of gastrointestinal symptoms, and peripheral eosinophilia is confirmed by the presence of eosinophilic infiltration of the gastrointestinal tract or ascites with a predominance of eosinophils, after the exclusion of other causes of eosinophilia. Automated cell counting analysis of the ascitic fluid can wrongly identify eosinophils as neutrophils, which can delay the diagnosis.

Monitoramento de matérias estranhas em polpas de tomate, goiaba, manga e morango adquiridas no comércio durante as estações do ano

Fruit-derived products sold in Brazil and for exportation are required to comply with the quality and safety standards. These products and, among them, the fruit pulps may contain extraneous materials due to the inappropriate conditions or practices during their production, storage and distribution, including filth, decomposed material and miscellaneous materials. This study aimed at evaluating the sanitary conditions(regarding to extraneous materials) of fruit pulps sold in the Great Sao Paulo, during the four seasons of 2010. This investigation analyzed 115 tomato pulp, 93 guava pulp, 99 strawberry pulp and 89 mango pulp by means of the techniques described in the AOAC, 18th, 2005, Chapter 16 - Extraneous Materials: Isolation. Insect fragments were the most frequent filth category detected in the pulps (in 93 % of guava and strawberry, 77 % of tomato and 48 % of mango samples), followed by the rodent hair (in 24 % of tomato, in 3 % of guava, in 1 % of strawberry and in 0.5 % of mango samples). The occurrence of miteswas mostly frequent in strawberry samples (33 %). This study indicated that the majority of the analyzed pulps showed satisfactory sanitary conditions, evidencing that the Good Manufacturing Practices was adopted by the productive sector. (AU) Os produtos derivados de frutas comercializados no Brasil e os exportados exigem do setor produtivo oatendimento aos padroes de qualidade e seguranca. Esses produtos, dentre eles, as polpas de frutas podemconter materias estranhas em funcao de condicoes ou praticas inadequadas de producao, armazenamento oudistribuicao, incluindo-se sujidades, material decomposto e materiais diversos. No presente estudo foramavaliadas as condicoes sanitarias (presenca de materias estranhas) de polpas de frutas comercializadas naGrande Sao Paulo, durante as quatro estacoes do ano de 2010. Foram analisadas 115 amostras de polpade tomate, 93 de polpa de goiaba, 99 de polpa de morango e 89 polpas de manga, empregando-se astecnicas descritas na AOAC, 18 ed, 2005, Capitulo 16 - Materias Estranhas: Isolamento. Os fragmentosde insetos foram detectados na maior porcentagem de amostras (em 93 % de goiaba e de morango, em77 % de tomate e 48 % de manga), seguidos de pelos de roedor (24 % em tomate, 3 % em goiaba, 1 %em morango e 0,5 % em manga). Os acaros foram mais frequentes nas amostras de morango (33 %). Nogeral, a maioria das polpas analisadas apresentou condicoes sanitarias satisfatorias, o que indica que asBoas Praticas de Fabricacao foram adotadas pelo setor produtivo.(AU)Fruit-derived products sold in Brazil and for exportation are required to comply with the quality and safety standards. These products and, among them, the fruit pulps may contain extraneous materials due to the inappropriate conditions or practices during their production, storage and distribution, including filth, decomposed material and miscellaneous materials. This study aimed at evaluating the sanitary conditions (regarding to extraneous materials) of fruit pulps sold in the Great Sao Paulo, during the four seasons of 2010. This investigation analyzed 115 tomato pulp, 93 guava pulp, 99 strawberry pulp and 89 mango pulp by means of the techniques described in the AOAC, 18th, 2005, Chapter 16 - Extraneous Materials: Isolation. Insect fragments were the most frequent filth category detected in the pulps (in 93 % of guava and strawberry, 77 % of tomato and 48 % of mango samples), followed by the rodent hair (in 24 % of tomato, in 3 % of guava, in 1 % of strawberry and in 0.5 % of mango samples). The occurrence of mites was mostly frequent in strawberry samples (33 %). This study indicated that the majority of the analyzed pulps showed satisfactory sanitary conditions, evidencing that the Good Manufacturing Practices was adopted by the productive sector.