Diet patterns and the incidence of age-related macular degeneration in the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among the elderly. OBJECTIVE: This study aimed to determine the association between dietary patterns and food groups (used to make them) with the 18-year incidence of AMD. METHODS: ARIC (Atherosclerosis Risk in Communities) participants who showed change in AMD lesions between retinal photographs taken at visit 3 and visit 5 were graded side by side to determine incident AMD (any=144; early=117; late=27). A 66-line item food frequency questionnaire, administered at visit 1 and visit 3, was used to identify 29 food groups. Principal component analysis was used to derive dietary patterns from average food group servings. Logistic regression was used to estimate ORs and 95% CIs for incident AMD (any, early and late) by tertiles of dietary pattern scores, adjusted for age, race, education, total calories and smoking status. P-trend was estimated using continuous scores. RESULTS: Western (unhealthy) and Prudent (healthy) dietary patterns were identified. No significant associations were observed between either dietary pattern and incident any or incident early AMD. However, a threefold higher incidence of late AMD was observed among participants with a Western pattern score above, as compared with below, the median (OR=3.44 (95% CI 1.33 to 8.87), p-trend=0.014). The risk of developing late AMD was decreased, but not statistically significant, among participants with a Prudent pattern score above, as compared with below, the median (OR=0.51 (95% CI 0.22 to 1.18), p-trend=0.054). CONCLUSIONS: Diet patterns were not significantly associated with incident any or incident early AMD. However, consumption of a Western pattern diet may be a risk factor for development of late AMD.

Recommendations for cerebrospinal fluid analysis.

Diseases of the central nervous system (CNS) mean for the human organism a potentially dangerous situation. An investigation of cerebrospinal fluid (CSF) provides important information about a character of CNS impairment in the decision-making diagnostic and therapeutic algorithm. The authors present a brief overview of available cerebrospinal fluid assays, shortened indication criteria, a recommended algorithm of CSF assessment in different suspected diseases, and a view of the external quality system. The whole portfolio of obtainable CSF methodology is further subdivided according to the adequate choice into the first and inevitable basic routine panel, and following complicated analyses of highly specialized character. The basic panel is considered for standard laboratories, the complete specialized assessment should be provided by a super-consulting laboratory.

Vitamin D Status and Prevalent Early Age-Related Macular Degeneration in African Americans and Caucasians: The Atherosclerosis Risk in Communities (ARIC) Study.

OBJECTIVES: Vitamin D status has been hypothesized to protect against development of early age-related macular degeneration (AMD) via its anti-inflammatory properties and its possible beneficial influence on blood pressure control. We investigated the association between vitamin D status and prevalent early AMD in a community-based cohort. DESIGN: This was a cross-sectional study. SETTING: This was a secondary data analysis of already existing data from the Atherosclerosis Risk in Communities Study (ARIC) cohort collected from 1990 to 1995. PARTICIPANTS: There were 9,734 (7,779 Caucasians, 1,955 African American) ARIC participants (aged 46 to 70 at visit 2 [1990-1992]) with 25(OH)D data available at visit 2, AMD assessment at visit 3 (1993-1995), and complete covariate data. MEASUREMENTS: Vitamin D status was assessed with serum 25-hydroxyvitamin D (25(OH)D) concentrations from bloods drawn at visit 2. Prevalent, early AMD (n=511) was assessed at visit 3 (1993-95) with nonmydriatic retinal photographs of one randomly chosen eye. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for early AMD by categories of 25(OH)D in nmol/L (deficient <30, inadequate 30-<50, and two categories of adequate status: 50-<75 and ≥75). Linear trend was estimated using continuous 25(OH)D concentrations. ORs were adjusted for age, race, and smoking status. We further adjusted for hypertension status to examine if vitamin D status influenced early AMD via its effects on blood pressure. Exploratory analyses of effect modification by age, sex, race and high risk genotypes [Y402H complement factor H (CFH) rs1061170 and the A69S age-related maculopathy susceptibility 2 (ARMS2) rs10490924 polymorphisms] were conducted. RESULTS: The prevalence of early AMD was 5%, and 5% of participants were vitamin D deficient. The adjusted OR (95% CIs) for early AMD among those with adequate (≥75 nmol/L) compared to deficient (<30 nmol/L) vitamin D status was 0.94 (0.59-1.50), p-trend=0.86. Further adjustment for hypertension status did not influence results (OR [95% CI]=0.95 [0.59-1.52], p-trend=0.84). Results did not vary significantly by age, race, sex, early AMD subtype (soft drusen or retinal pigment epithelium depigmentation), or ARMS2 genotype. Results did not vary significantly by CFH genotype in African Americans. The p for multiplicative interaction between 25(OH)D and CFH genotype was 0.06 in Caucasians, but OR [95% CIs] for AMD by vitamin D status were similar in each CFH genotype and not statistically significant. CONCLUSIONS: Vitamin D status was not associated with early AMD in this cohort sample.

MicroRNAs in urine supernatant as potential non-invasive markers for bladder cancer detection.

Urinary bladder carcinoma contributes to 4% of newly diagnosed oncological diseases in the Czech Republic. Biomarkers for its early non-invasive detection are therefore highly desirable. Urine seems to be an ideal source of such biomarkers due to the content of cell-free nucleic acids, especially microRNAs (miRNAs).To find potential biomarkers among miRNAs in urine supernatant, we examined in total 109 individuals (36 controls and 73 bladder cancer patients) in three phases. In the first - discovery - phase, microarray cards with 381 miRNAs were used for miRNA analysis of 13 controls and 46 bladder cancer patients. In the second - verification - phase, the results of this first phase were verified on the same groups of subjects by single-target qPCR assays for the selected miRNAs. For the third - validation - phase, new independent samples of urine supernatant (23 controls and 27 bladder cancer patients) were analyzed using single-target qPCR assays for 13 verified in the previous phase. The results of all phases were normalized to miR-191, miR-28-3p, and miR-200b, which were selected as suitable for our study by the qBase+®.We found that miR-125b, miR-30b, miR-204, miR-99a, and miR-532-3p are significantly down-regulated in patients' urine supernatant. In our experiments, the analysis of miR-125 levels provided the highest AUC (0.801) with 95.65% specificity and 59.26% sensitivity, the analysis of miR-99a lead to AUC (0.738) with 82.61% specificity and 74.07% sensitivity. We demonstrate that levels of these miRNAs could potentially serve as promising diagnostic markers for the non-invasive diagnostics of bladder cancer.

Safety and immunogenicity of a glycoprotein D genital herpes vaccine in healthy girls 10-17 years of age: results from a randomised, controlled, double-blind trial.

OBJECTIVE: The investigational AS04-adjuvanted herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) subunit prophylactic vaccine ('HSV vaccine'; GlaxoSmithKline Vaccines) has been shown to be well tolerated in adults, but limited data exist for pre-teen and adolescent girls, a likely target population. The primary objective of this study was to compare the occurrence of serious adverse events (SAEs) over 12 months between HSV vaccine recipients and saline recipients (placebo control group) in pre-teen and adolescent girls. The immunogenicity of the HSV vaccine was also assessed. METHODS: Healthy girls aged 10-17 years, stratified by age (10-15 years; 16-17 years), were randomised 2:1:1 to receive the HSV vaccine, a hepatitis A vaccine (Havrix™; HAV control) or placebo (saline) according to a 0-, 1-, 6-month schedule. Participants and study personnel not involved in the preparation or administration of vaccines were blinded to treatment. Safety and immunogenicity analyses were performed overall and by age (10-15 years; 16-17 years) and HSV serostatus. RESULTS: No statistically significant difference in the percentage of subjects with SAEs was observed between the HSV and saline group, or between the HSV and pooled control (HAV and saline) groups. The HSV vaccine was well tolerated, although a higher incidence of solicited local symptoms was observed in the HSV group than in the control group. Neither age nor HSV serostatus at the time of study entry had an impact on the safety profile of this vaccine. The HSV vaccine was immunogenic regardless of pre-vaccination HSV serostatus. Higher anti-gD geometric mean concentrations were observed in HSV-1 seropositive participants than in HSV-1 seronegative participants. CONCLUSION: The HSV vaccine had an acceptable safety profile, and was well tolerated and immunogenic when administered to girls aged 10-17 years regardless of age or HSV pre-vaccination serostatus.

Prediction of recurrence in low and intermediate risk non-muscle invasive bladder cancer by real-time quantitative PCR analysis: cDNA microarray results.

The aim of the study was to define specific genetic profile in Ta and T1 urinary bladder carcinoma patients with and without recurrence by gene expression microarrays. Eleven patients with the time to recurrence shorter than one year (patients with recurrence) and 11 patients with time to recurrence longer than 4 years (patients without recurrence) were enrolled. Data from microarrays were subjected to a panel of statistical analyses to identify bladder cancer recurrence-associated gene signatures. Initial screening using the GeneSpring and Bioconductor software tools revealed a putative set 47 genes differing in gene expression in both groups. After the validation, 33 genes manifested significant differences between both groups. The significant expression was observed in the group of patients without recurrence by 30 genes of which the highest differences were detected by ANXA1, ARHGEF4, FLJ32252, GNE, NINJ1, PRICKLE1, PSAT1, RNASE1, SPTAN1, SYNGR1, TNFSF15, TSPAN1, and WDR34. These genes code for signal transduction, vascular remodeling and vascular endothelial growth inhibition mainly. In the group with recurrence, 3 genes had significant differences, the highest differences were identified by two genes (PLOD2 and WDR72). Loci of genes with significant changes of gene expression were located on characteristic chromosomes for bladder cancer: 7 loci on chromosome 9, 8 loci on chromosomes 1, 2, 3, 12,14,15,16, and 22. We have selected and validated 15 genes that are differentially expressed in superficial bladder cancer. We hope that this cohort of genes will serve as a promising pool of candidate biomarkers for early stage bladder cancer. Our results indicate that it may be possible to identify patients with a low and high risk of disease recurrence at an early stage using a molecular profile.

Endothelial progenitors encapsulated in bioartificial niches are insulated from systemic cytotoxicity and are angiogenesis competent.

Intrinsic stem cells (SC) participate in tissue remodeling and regeneration in various diseases and following toxic insults. Failure of tissue regeneration is in part attributed to lack of SC protection from toxic stress of noxious stimuli, thus prompting intense research efforts to develop strategies for SC protection and functional preservation for in vivo delivery. One strategy is creation of artificial SC niches in an attempt to mimic the requirements of endogenous SC niches by generating scaffolds with properties of extracellular matrix. Here, we investigated the use of hyaluronic acid (HA) hydrogels as an artificial SC niche and examined regenerative capabilities of encapsulated embryonic endothelial progenitor cells (eEPC) in three different in vivo models. Hydrogel-encapsulated eEPC demonstrated improved resistance to toxic insult (adriamycin) in vitro, thus prompting in vivo studies. Implantation of HA hydrogels containing eEPC to mice with adriamycin nephropathy or renal ischemia resulted in eEPC mobilization to injured kidneys (and to a lesser extent to the spleen) and improvement of renal function, which was equal or superior to adoptively transferred EPC by intravenous infusion. In mice with hindlimb ischemia, EPC encapsulated in HA hydrogels dramatically accelerated the recovery of collateral circulation with the efficacy superior to intravenous infusion of EPC. In conclusion, HA hydrogels protect eEPC against adriamycin cytotoxicity and implantation of eEPC encapsulated in HA hydrogels supports renal regeneration in ischemic and cytotoxic (adriamycin) nephropathy and neovascularization of ischemic hindlimb, thus establishing their functional competence and superior capabilities to deliver stem cells stored in and released from this bioartificial niche.

New laboratory markers in diagnosis of alzheimer dementia.

OBJECTIVES: The aim of our work was to assess the role of tau protein, beta amyloid and cystatin C in diagnosis of Alzheimer dementia (AD) and other neurodegenerative diseases (NDs). METHODS: The levels of tau protein, beta amyloid and cystatin C were assessed in a set of 79 patients with ND (38 men and 41 women; aged 22-90 years; mean, 61.6 +/- 15.6 years) and in a control group of 79 subjects with a healthy central nervous system (38 men and 41 women; aged 20-91 years; mean, 61.5 +/- 15.1 years). RESULTS: When compared with the subjects in the control group, a statistically significant decrease in tau protein levels was found in patients with ND, an increase in tau protein levels in patients with AD and an increase in cystatin C cerebrospinal fluid/serum index in the ND + AD group. DISCUSSION: Our work only confirmed the previously reported results in part. Although tau protein seems to be a quite reliable marker of AD, the role of beta amyloid in AD diagnosis remains at the least questionable. In the case of cystatin C, our results would seem to confirm the views of certain authors that cystatin C will probably not become a new 'revolutionary' marker contributing to differential diagnostics.

[Persistent diarrhoea, hypotension, polyneuropathy]. / Perzistentní prujmy, hypotenze a polyneuropatie.

We present a case report of a 59-year-old man with a history of arterial hypertension and excision of malignant melanoma. He was admitted to the hospital because of two months history of diarrhoea, weight loss and circulatory collapse. In addition, the patient suffered from marked vegetative instability with symptomatic hypotension, polyneuropathy and progression of renal insufficiency, without proteinuria. Complex examination did not reveal neoplasms, endocrine, autoimmune, infectious or neurodegenerative disorders. A serial biopsy of colon failed to provide a clue to the diagnosis. However, AA amyloidosis was found on the kidney biopsy. Neither chronic inflammation nor malignancy was revealed and, hence, no causal treatment could have been established. The patient died from multiple organ failure. The autopsy confirmed systemic AA amyloidosis. The triad consisting ofdiarrhoea, polyneuropathy and hypotension should rise the suspicion on amyloidosis.

Influence of melatonin pretreatment and preconditioning by hypobaric hypoxia on the development of cortical photothrombotic ischemic lesion.

Photothrombotic model of ischemia (PT) is based on free radical-mediated endothelial dysfunction followed by thrombosis. Free radicals are also involved in hypoxic preconditioning. We tested the sensitivity of PT to preconditioning with hypobaric hypoxia and to pretreatment with melatonin. In adult Wistar rats, after intravenous application of Rose Bengal, a stereo-tactically defined spot on the denuded skull was irradiated by a laser for 9 min. The first experimental group underwent hypobaric hypoxia three days before irradiation. In the second experimental group, melatonin was applied intraperitoneally one hour before irradiation. Three days after irradiation, animals were sacrificed, the brains perfused, and stained with TTC. Ischemic lesions were divided into grades (I, II, III). In the control group (where no manipulation preceded photothrombosis), most animals displayed deep damage involving the striatum (grade III). The group pre-exposed to hypoxia showed similar results. Only 28.57 % of the melatonin pretreated animals exhibited grade III lesions, and in 57.14 % no signs of lesions were detected. Pre-exposure to hypoxia was not protective in our model. Pretreatment with melatonin lead to a significant reduction of the number of large ischemic lesions. This result is probably caused by protection of endothelial cells by melatonin.

Association of PAX5 expression with clinical outcome in patients with TaT1 transitional cell carcinoma of the bladder.

OBJECTIVES: To assess the frequency and intensity of PAX5 gene messenger ribonucleic acid (mRNA) expression in TaT1 bladder cancer tissue, as well as its correlation with clinicopathologic variables and patient outcome. METHODS: The RNA expression of PAX5 was evaluated with reverse transcriptase polymerase chain reaction in the tumor tissue of 75 patients with stage TaT1 bladder cancer treated with transurethral resection. Patients were observed with cystoscopy and urinary cytologic evaluation. The association between PAX5 expression and clinicopathologic variables and patient outcome was evaluated. Benign urothelium from 8 patients with benign prostatic hyperplasia was obtained. These patients were used as a control group. RESULTS: PAX5 expression was found in 62 patients with bladder cancer (82.7%) but in no patient from the control group. High PAX5 expression (greater than 0.2) was confirmed in 19 patients (25.3%). No significant relationship was observed between quantity of PAX5 expression and clinicopathologic variables. The 3-year recurrence-free and progression-free survival rates in highly positive patients were 13.2% and 71.6%, compared with 40.6% and 92.8%, respectively, in patients with weak or negative expression (log-rank test, P = 0.0075, P = 0.022). Multivariate Cox proportional hazard model analysis identified PAX5 expression as an independent predictor of tumor recurrence. CONCLUSIONS: PAX5 gene expression is a frequent finding in superficial transitional cell carcinoma of the bladder. High levels of PAX5 are associated with poorer recurrence-free and progression-free survival rates. Moreover, PAX5 expression was found to be an independent prognostic factor for recurrence-free survival by a multivariate analysis.

[Expression of PAX2 and PAX8 genes in conventional type of renal carcinoma and their role in the tumor prognosis]. / Exprese genu PAX2 a PAX8 v konvencním typu renálního karcinomu a jejich role v prognostice tohoto onemocnení.

BACKGROUND: Sporadic renal cell carcinoma is one of the most common kidney malignancies in adults (85%). According to the IARC (The International Agency of Research on Cancer) Czech Republic has the first world position in the incidence and mortality for RCC. The prognosis of RCC is very poor because of high mortality around 70 to 50% and unpredictable progression after tumor removal. More precise molecular prognostic markers are required. Genes PAX2 and PAX8 control cell division during embryonic development and plays crucial role in tumor development because of stimulation of cell proliferation and/or inhibition of apoptotic program. METHODS AND RESULTS: Our RCC sample collection contains 64 tumor samples and 10 "normal" renal samples extracted from the affected kidney. mRNA was isolated from all samples and converted into cDNA. Expression of PAX genes was analyzed by using relative quantification real-time PCR with TaqMan labelled probe and GAPDH gene as an endogenous control. CONCLUSIONS: Expression of PAX2 gene was found in 97% and expression of PAX8 gene was found in 89% of analyzed tumor samples. The expression of both target genes was found in all "normal" renal samples. The level of expression of both PAX genes was very variable with the range from hundred times lower to forty times higher in comparison with the expression of chosen endogenous control. There were found no correlations between the expression of target genes and clinical-histological markers. These results do not have prognostic value yet because of short duration of patient observation. Follow-up clinical data are essential for completion of this research.

[Molecular nature of renal tumours of adults]. / Molekulární podstata maligních nádoru ledvin dospelého veku.

Significant progress has been achieved recently in the cytogenetic and molecular research of the kidney parenchymal tumors which incidence has been steadily increasing in the developed countries. Renal cancer is an important clinical problem, still without effective therapy. The accuracy of current diagnosis, prognosis of the disease and the effectiveness of the treatment are limited by the poor understanding of its cytogenetic and molecular pathogenic mechanisms. In this review we summarize up to date cytogenetic alterations and gene expression profiles of the most important tumor genes, focusing at the classification of parenchyma tumors of adult patients.

The expression of PAX5, p53 immunohistochemistry and p53 mutation analysis in superficial bladder carcinoma tissue. Correlation with pathological findings and clinical outcome.

OBJECTIVES: The expression pattern of PAX5 in the tissue of superficial bladder transitional cell carcinoma (TCC), its prognostic value and its correlation with p53 immunohistochemistry and p53 mutation analysis were evaluated. METHODS: Study comprised 61 patients with histologically confirmed superficial bladder TCC. Expression level of PAX5 mRNA was investigated using reverse transcriptase-polymerase chain reaction (RT-PCR) and determined semiquantitatively. The presence of p53 mutations was determined by SSCP and confirmed by direct sequencing. The p53 immunohistochemistry was performed with DO1 antibody and semiquantitatively evaluated using HSCORE (HS) method. As the control group for the evaluation of the PAX5 expression served 8 men with benign prostatic hyperplasia. RESULTS: PAX5 expression was found in 50 patients with bladder TCC but in no patient from the control group. Its quantity however correlated neither with the stage nor with the grade of the tumor. P53 mutation was confirmed only in 1 patient with pTaG2 tumor in exon 5 (deletion of proline 128). On the contrary, positive immunohistochemical staining of p53 was detected in most patients. Using the cutoff value of HS 200, 56.9% of patients showed p53 overexpression. Quantity of p53 immunochistochemical positivity did not correlate with the quantity of PAX5 expression. Using the cutoff values of HS 200 for p53 and of 0.2 for PAX5, 7 of 8 patients with future progression had p53 and 4 had PAX5 overexpression respectively. CONCLUSION: The expression of gene PAX5 is a frequent event in superficial TCC of the bladder.

[Molecular genetics of Wilms' tumor]. / Molekulární genetika Wilmsova tumoru.

Molecular genetics of the Wilms' tumor plays an important role in the elucidation of the genetic etiology of the tumor disease generally. Contrary to the genesis of retinoblastoma, where a single gene is inactivated by two hits, the biological signalling pathways determining the origin of the Wilms' tumor are more complex and several genes in several loci may participate. Formation of the Wilms' tumor is accompanied with the most frequent genetic alteration, which is the loss of heterozygosity on the short arm of chromosome 11. It indicates inactivation of one or several tumor suppressor genes located at 11p region. The most studied gene of the Wilms' tumor is WT1 gene, which has been cloned and sequenced. Biological function of WT1 protein is complex one and it requires probably an interaction with other proteins, DNA and also RNA. The development of the tumor determines not only the genetic changes, but also epigenetic changes, e.g., hypermethylation of promoter and genome imprinting.

Methylation changes in promoter and enhancer regions of the WT1 gene in Wilms' tumours.

Although the WT1 gene has been implicated in the aetiology of Wilms' tumour, mutations in WT1 are found only in minority of the tumours. DNA methylation of regulatory elements represents another possibility of modulation of gene expression. We studied methylation in the promoter and enhancer regions of the WT1 gene in 34 Wilms' tumour patients by the polymerase chain reaction on HpaII-digested DNA and by the bisulphite method. No methylation was detected in the promoter region in either tumour or normal kidney or blood DNA samples. In contrast, a HpaII site in the enhancer region was at least partially methylated in normal kidney and blood DNA samples and in about one-third of the tumours, while the majority of tumours showed no methylation. The differential methylation in the enhancer region of the WT1 gene may indicate that methylation of this element can play a role in the regulation of this gene.

[DNA methylation and neoplasms]. / Metylace DNA a nádorová onemocnení.

DNA methylation and acetylation of histone proteins represent two global mechanisms controlling the gene expression. DNA methylation profiles alter during the development of the organism and during progression of neoplasia. Three types of alterations of the DNA methylation profiles were observed in the tumor cells: hypomethylation, hypermethylation and the loss of imprinting. Beside the intra-gene mutation and the heterozygosity absence, DNA methylation can be understood as the third mechanism of tumor-suppressor gene inactivation in the genesis of neoplasia. Our review article brings recent findings and hypotheses on the role of DNA methylation in the carcinogenesis and its possible application in the diagnostics and therapy of the malignant proliferation.

Use and evaluation of the Czech version of the SF-36 questionnaire self-reported health status of medical students.

SF-36 questionnaires were completed by 231 medical students of the Faculty of Medicine in Hradec Králové (1997, 1998). Results of measurements of eight health dimensions are presented here. Significantly lower values for bodily pain were found in the group of overweight students. Students with some reported cured diseases have significantly lower values for bodily pain and general health dimensions in comparison with students without any reported disease. In our sample a high rate of non-smokers (86.4% men and 93.6% women) and low rate of students with BMI > 25 (18.4% men and 3.8% women) were found. About 30% of respondents reported one or more cured diseases. In addition to the SF-36 questionnaire, students in 1998 completed also a special one-page form (3). The one-page form enabled direct estimates of the eight dimensions of the health status on a scale from 0% to 100%. This study compares the results of measurement of the health status for both instruments. Differences found here are compared and discussed with similar comparisons in an American study (3). Results in both studies are similar but not the same. An indirect measurement of health status with specific questions in the SF-36 is more objective than a direct measurement with the one-page form. Nevertheless, the SF-36 is limited in the number of possible answers for some dimensions (RP, RE). In that case, our results indicate that a percentage scale from the one-page form seems better. Additionally this study compares the results of the SF-36 in Czech medical students with comparable samples from other three European countries. On average, the health dimensions of SF-36 in Czech medical students achieved the worst values in comparison with samples from Switzerland, Germany and Great Britain.

Oncogene amplification and expression in pediatric solid tumors.

Oncogene amplification and expression and their mutual relationship was analyzed in 92 pediatric tumors by Southern and Northern blot hybridization with N-MYC, ERB A, ERB B, N-RAS and Shb probes. Amplification and overexpression was associated with more advanced clinical stages of tumor, especially in neuroblastomas, rhabdomyosarcomas and ganglioneuroblastomas. The most frequent alteration observed was N-MYC amplification together with overexpression. N-RAS amplification was not detected, while the overexpression of this oncogene was found in 3 cases. Neither amplification nor overexpression was revealed in any specimen of hepatoblastoma or hepatocellular carcinoma. We suggest that oncogenes overexpression provides more accurate prognostic information than amplification.

Allele loss in Wilms tumors of chromosome arms 11q, 16q, and 22q correlate with clinicopathological parameters.

An extended analysis for loss of heterozygosity (LOH) on eight chromosomes was conducted in a series of 82 Wilms tumors. Observed rates of allele loss were: 9.5% (1p), 5% (4q), 6% (6p), 3% (7p), 9.8% (11q), 28% (11p15), 13.4% (16q), 8.8% (18p), and 13.8% (22q). Known regions of frequent allele loss on chromosome arms 1p, 11p15, and 16q were analyzed with a series of markers, but their size could not be narrowed down to smaller intervals, making any positional cloning effort difficult. In contrast to most previous studies, several tumors exhibited allele loss for multiple chromosomes, suggesting an important role for genome instability in a subset of tumors. Comparison with clinical data revealed a possible prognostic significance, especially for LOH on chromosome arms 11q and 22q with high frequencies of anaplastic tumors, tumor recurrence, and fatal outcome. Similarly, LOH 16q was associated with anaplastic and recurrent tumors. These markers may be helpful in the future for selecting high-risk tumors for modified therapeutic regimens.