p53 expression and subcellular survivin localization improve the diagnosis and prognosis of patients with diffuse astrocytic tumors

Purpose

Diffuse astrocytic tumors are the most frequently occurring primary central nervous system (CNS) tumors. Their histological sub-classification into diffuse astrocytoma (DA), anaplastic astrocytoma (AA) and glioblastoma (GB) is challenging and the available prognostic factors are limited to age and tumor subtype. Biomarkers that may improve the histological sub-classification and/or serve as prognostic factors are, therefore, urgently needed. The relationship between survivin and p53 in diffuse astrocytic tumor progression and survival is currently unclear. Here, we aimed to assess the relevance of these proteins in the accuracy of the histological sub-classification of these tumors and their respective treatment responses.

Methods

One hundred and thirty-three formalin-fixed paraffin-embedded diffuse astrocytic tumor samples were included. The tumor samples were histologically reviewed and subsequently assessed for p53 and survivin expression and the presence of the IDH R132H mutation by immunohistochemistry. p53 expression levels and survivin subcellular localization patterns were correlated with histological classification and clinical outcome.

Results

We found that age and histological subtype were the only features with a prognostic impact. In addition, we found that high p53 expression levels and a nuclear survivin localization correlated with the AA subtype, whereas cytoplasmic survivin localization correlated with the GB subtype. We also found that patients carrying tumors with a high cytoplasmic survivin expression, a high nuclear survivin expression or a high p53 expression, and who did not receive radiotherapy, exhibited poorer short-term and long-term overall survival rates.

Conclusions

Our data suggest that subcellular survivin localization and p53 expression may be employed as valuable tools to improve the accuracy of the histological sub-classification of diffuse astrocytic tumors. Patients whose tumors overexpress these proteins may benefit from radiotherapy, irrespective age and/or histological classification.

     

Development of a Model to Predict Invasiveness in Ductal Carcinoma In Situ Diagnosed by Percutaneous Biopsy—Original Study and Critical Evaluation of the Literature

Background

Approximately 30% of ductal carcinoma in situ (DCIS) cases have an invasive component discovered on the final analysis that could affect surgical management. The aims of the present study were to determine the risk factors associated with the underestimation of DCIS and to develop a model to predict the probability of invasiveness.

ABO blood group in Amerindians from Brazilian Amazon

BACKGROUND: The Parakan? is a group of Indians with cultural similarities to the extinct Tupi group. They are an isolated native population from East Brazilian Amazon. A number of different O alleles have been found at the blood group ABO locus in populations of several ethnic origins (Caucasians, Blacks, Amerindians). AIM: The present study describes the ABO blood group polymorphism gene of the Parakan? Indians. The Amerindian group was carefully selected for racial background. SUBJECT AND METHODS: The blood group polymorphism was analysed in genomic DNA from 62 Parakan? Indians. We determined the 261G deletion, the T646A and C771T mutations described in O(1variant) and the G542A substitution, using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism). RESULTS: All Amerindians studied were homozygous for the 261G deletion. The frequencies of the T646A and C771T mutations in Parakan?s (0.65) were lower than that observed in Kayapo, Yanomama and Arara Indians (0.91) (chi (2) = 18.24; p-v < 0.001. The G542A substitution in Parakan?s was also lower (0.22) than in other tribes (0.42) (chi(2) = 9.73; p-v = 0.001). CONCLUSIONS: The different O alleles including the G542A mutation are not distributed homogeneously among all Amazonian Amerindians. Our results are in agreement with other genetic markers studied previously in Parakan? Indians, whose distinct genetic pattern differs from Europeans and even from other Amerindians.     

Microbiological quality of " ice, ice cream. sorbet" sold on the streets of Phnom Penh; April 1996-April 1997

A study of the microbiological quality of ice lice creams/sorbets sold on the streets of Phnom Penh city was conducted from April 1996 to April 1997. Socio-demographic and environmental characteristics with two ice/ice creams samples were collected from vendors selected in the city. A total of 105 vendors and 210 ice/ice creams samples were randomly selected for the study period. Ice/ice cream vendors in the streets of Phnom Penh were adults (mean age: 28 years old) with a male predominance (86.5%). Mean educational level of vendors was 5 years with no training in mass catering. Most ice creams and sorbets (81.7%) were made using traditional methods. Microbiological analysis performed in the laboratory of Pasteur Institute of Cambodia indicated the poor bacteriological quality of the samples. The proportions of samples classified unsafe according to microbiological criteria were 83.3% for total bacterial count at 30 degrees C, 70% for total coliforms, 30% for faecal coliforms, 12.2% for Staphylococcus aureus and 1.9% for presence of Salmonella spp. These bacterial results suggest that many other food products sold in the streets may be similarly poor. Safety measures should be undertaken to avoid potential threats. Regulation of the street food sector should be part of a larger strategy for enhanced food safety and environmental quality in the city.     

Prognosefaktoren bei differenzierten Schilddrüsenkarzinomen

Zusammenfassung Der Einflu? etablierter und noch nicht abschlie?end beurteilbarer Parameter auf die Prognose von Follikelzellkarzinomen der Schilddrüse wird dargestellt. Das Spektrum der in dieser umfangreichen Literaturanalyse enthaltenen pathologischen und biologischen Faktoren reicht von klassischen Prognosemerkmalen wie Alter, Geschlecht und Tumorstadium bis hin zur Mutation bzw. Aktivierung oder Inaktivierung von Tumorsuppressor-Genen, Metastasierungs-assoziierten Genen und Adh?sionsmolekülen.      

The Human RNA Helicase A (DDX9) Gene Maps to the Prostate Cancer Susceptibility Locus at Chromosome Band 1q25 and Its Pseudogene (DDX9P) to 13q22, Respectively

RNA helicase A is the homolog of the Drosophila maleless protein, an essential factor involved in dosage compensation, and plays a crucial role in early development in mammals. Here, we have mapped the human RNA helicase A (DDX9) gene to the major susceptibility locus for prostate cancer at chromosome band 1q25, and its pseudogene (DDX9P) to the band 13q22 by fluorescence in situ hybridization, somatic cell hybrid analysis, and assignment of YAC clones, respectively.     

Intravascular brachytherapy physics: report of the AAPM Radiation Therapy Committee Task Group no. 60. American Association of Physicists in Medicine

Recent preclinical and clinical studies indicate that irradiation using ionizing radiation in the dose range of 15 to 30 Gy may reduce the occurrence of restenosis in patients who have undergone an angioplasty. Several delivery systems of intravascular brachytherapy have been developed to deliver radiation doses in this range with minimal normal tissue toxicity. In late 1995 the American Association of Physicists in Medicine (AAPM) formed a task group to investigate these issues and to report the current state of the art of intravascular brachytherapy physics. The report of this task group is presented here.     

Significance of trisomy 7 and 12 in thyroid lesions with follicular differentiation: a cytogenetic and in situ hybridization study

In a group of benign and malignant follicular thyroid lesions, previously analyzed by conventional cytogenetics, single- and double-target fluorescence in situ hybridization studies with pericentromeric probes specific for chromosomes 7 and 12 were performed, by using isolated nuclei from paraffin-embedded specimens of: 11 goiters, 21 adenomas, 9 follicular carcinomas, and adjacent normal thyroid tissue. Nonisotopic in situ hybridization with the same probes was used in 4-microm histologic sections of four follicular carcinomas. By fluorescence in situ hybridization analysis, the percentage of goiters, adenomas, and follicular carcinomas with gains of No. 7 was 18.2%, 52.4%, and 66.0%, respectively, and with gains of No. 12 was 9.0%, 42.9%, and 66.0%, respectively. The percentage of the same lesions (goiters, adenomas, carcinomas) exhibiting polysomies of No. 7 and No. 12, as assessed by cytogenetic analysis, was 5.0% and 0.0%, 20.0% and 20.0%, and 15.8% and 10.5%, respectively. Numerical alterations of these chromosomes were not observed in normal tissue. These findings reveal that gain of chromosomes 7 and 12 is a characteristic of the morphologically altered thyroid tissue; polysomies of chromosomes 7 and 12 are more frequent in thyroid lesions than it can be detected by conventional cytogenetic studies; the increasing frequency of polysomies of chromosomes 7 and 12 from hyperplastic lesions to benign and malignant tumors seem to substantiate the existence of a multistep pathway, ie, normal thyroid --> goiter --> adenoma --> follicular carcinoma in the pathogenesis of some thyroid neoplasms.     

Long-term evolution of the acute tubular necrosis (ATN) induced by glycerol: role of myofibroblasts and macrophages

Late structural changes such as interstitial fibrosis in the renal cortex and tubular atrophy have been detected after severe acute tubular necrosis (ATN). The aim of this study was to investigate the expression of fibronectin, alpha-smooth muscle actin and macrophages during the evolution of the ATN induced by glycerol and their relationship with the late structural changes observed in the kidneys of these animals. Forty-nine male Wistar rats were injected with a 50% glycerol solution, 8 mL/kg (4 mL/kg applied i.m. to each hind leg) and 14 with 0.15 m NaCl solution. Before glycerol injection on day 1, water was removed for 17 h. Blood and urine samples were collected 1 day after the injection to quantify sodium and creatinine. The animals were killed 5, 30 and 60 days after the injections and the kidneys removed for histological and immunohistochemical studies. The results of the histological and immunohistochemical studies were scored according to the extent of lesion or staining in the cortical tubulointerstitium, respectively. The percentage of tubulointerstitial lesions was determined by morphometry. Glycerol-injected rats presented a transitory increase in plasma creatinine levels and in fractional sodium excretion. The immunohistochemical studies showed increased fibronectin, alpha-smooth muscle actin (alpha-SM-actin), TGF-beta and ED-1 (macrophages) staining in the renal cortex from rats killed 5, 30 and 60 days after glycerol injection (P < 0.05) compared to control. The animals killed on day 30 and 60 also presented chronic lesions (fibrosis, tubular dilatation and atrophy) in the renal cortex, despite the recovery of renal function. Macrophages, TGF-beta and myofibroblasts may have contributed to the development of renal fibrosis in these rats.     

A prospective study of the morphological aspects of tumor involvement of the pulmonary vessels.

A prospective morphological study of tumor involvement of the pulmonary vessels (TIPV) was undertaken on 203 consecutive autopsy cases of malignancies. The lungs were removed as a block and 15 sections (3 from each lobe) were analyzed. Site of origin, histological type and staging of the tumor, topographic distribution of the tumor emboli in the lungs, right ventricular hypertrophy and dilatation, pulmonary infarct, pulmonary vascular sclerosis and lung metastases were recorded in each case. TIPV was detected in 84 (41.4%) cases, the highest frequency reported until now. In 28 cases, TIPV was considered to be the main cause of death. The breast, liver, and pancreas were primary sites in more than 50% of the cases in which TIPV was observed. TIPV was more prevalent in epithelial neoplasms and showed a strong correlation with advanced disease. There was no significant difference among topographic regions of the lungs. The cases with TIPV were correlated with a high frequency of right ventricular hypertrophy and dilatation, vascular sclerosis and pulmonary metastases but not with pulmonary infarcts.