A comparison of two models of follow-up care for adult survivors of childhood cancer.

PURPOSE: Few studies have compared follow-up-care models for adult survivors of childhood cancer (ASCCs), though choice of model could impact medical test adherence, and health-related quality of life (QOL). This study compared two follow-up-care models, cancer-center-based versus community-based, for ASCCs in Alberta, Canada, to determine which model would demonstrate greater ASCC adherence to guideline-recommended medical screening tests for late effects, QOL, physical symptoms, and adherence to yearly follow-up. METHODS: ASCC discharged to a community model (over 15 years) and those with comparable birth years (1973-1993) currently followed in a cancer center model were recruited via direct contact or multimedia campaign. Chart review identified chemotherapeutic and radiation exposures, and required medical late effect screening tests. ASCCs also completed questionnaires assessing QOL, physical symptoms, and follow-up behavior. RESULTS: One hundred fifty-six survivors participated (community (n = 86); cancer center (n = 70)). Primary analysis indicated that cancer center ASCCs guideline-recommended total test adherence percentage (Mdn = 85.4%) was significantly higher than the community model (Mdn = 29.2%, U = 3996.50, p < 0.0001). There was no significant difference in QOL for cancer center ASCCs (M = 83.85, SD = 20.55 versus M = 77.50, SD = 23.94; t (154) = 1.77, p = 0.078) compared to community-based ASCCs. Cancer center-based ASCCs endorsed from 0.4-7.1% fewer physical symptom clusters, and higher adherence to follow-up behavior in comparisons using effect sizes without p values. CONCLUSION: This study highlights the cancer center model's superiority for adherence to exposure-based medical late effect screening guidelines, cancer-specific follow-up behaviors, and the reporting of fewer physical complaints in ASCCs. IMPLICATIONS FOR CANCER SURVIVORS: ASCCs followed in a cancer center model likely benefit from earlier late-effects detection and opportunities for early intervention.

Genomic imbalances pinpoint potential oncogenes and tumor suppressors in Wilms tumors.

BACKGROUND: Wilms tumor (WT) has a not completely elucidated pathogenesis. DNA copy number alterations (CNAs) are common in cancer, and often define key pathogenic events. The aim of this work was to investigate CNAs in order to disclose new candidate genes for Wilms tumorigenesis. RESULTS: Array-CGH of 50 primary WTs without pre-chemotherapy revealed a few recurrent CNAs not previously reported, such as 7q and 20q gains, and 7p loss. Genomic amplifications were exclusively detected in 3 cases of WTs that later relapsed, which also exhibited an increased frequency of gains affecting a 16.2 Mb 1q21.1-q23.2 region, losses at 11p, 11q distal, and 16q, and WT1 deletions. Conversely, aneuploidies of chromosomes 13 and 19 were found only in WTs without further relapse. The 1q21.1-q23.2 gain associated with WT relapse harbours genes such as CHD1L, CRABP2, GJA8, MEX3A and MLLT11 that were found to be over-expressed in WTs. In addition, down-regulation of genes encompassed by focal deletions highlighted new potential tumor suppressors such as CNKSR1, MAN1C1, PAQR7 (1p36), TWIST1, SOSTDC1 (7p14.1-p12.2), BBOX and FIBIN (11p13), and PLCG2 (16q). CONCLUSION: This study confirmed the presence of CNAs previously related to WT and characterized new CNAs found only in few cases. The later were found in higher frequency in relapsed cases, suggesting that they could be associated with WT progression.

Effectiveness and outcomes of surgery for cerebral metastases.

INTRODUCTION: The main treatment modalities for single brain metastases are whole brain radiotherapy (WBRT), surgery and stereotactic radiosurgery. Current guidelines recommend complete surgical excision for single cerebral metastases and two randomised controlled trials (RCT) have also found survival benefit of surgery. However, a more recent RCT and a Cochrane review have challenged the effectiveness of surgery for cerebral metastases. This study aims to assess the effectiveness of surgery for cerebral metastases in current practice. MATERIALS AND METHODS: A retrospective review was performed for a single surgeon series of consecutive patients undergoing primary surgery for cerebral metastases between June 2005 and April 2010. The main outcome measure was the survival time after surgery. RESULTS: One hundred and twenty three patients (61 males, 62 females) were identified with a mean age of 58.4 years. Eighty three patients (67%) were under 65 years. The overall 30-day mortality rate was 2.4%. The overall median survival was 10 months. There were 26 (21%) breast cancers with median survival of 13.5 months, 32 (26%) NSCLC with 8.3 months, 24 (19%) melanomas with 6.7 months, 13 (11%) colorectal cancers with 6.4 months, and 11 (9%) renal cell cancers with 13.6 months. The differences were not significant (p > 0.05). However, when the breast cancer group was compared to the NSCLC group, the difference was significant (p = 0.005). The median survival differences were not significant (p > 0.05) with regard to the RPA class, the site (supratentorial or infratentorial) and the number of metastases (single or two). CONCLUSIONS: Median survival in this cohort was identical to those in the two RCTs that showed survival benefits from surgery. This was significantly longer than that (5.6 months) in the single series demonstrating no benefit. Therefore, our results support the previous evidence of improved outcomes with surgery.

Magneto-optical stokes polarimetry and nanostructured magnetic materials.

Stokes parameters fully characterize the polarization state of light in an experimentally accessible manner. Photoelastic modulator (PEM) based Stokes polarimetry offers a very high sensitivity which is particularly suitable for the investigation of the magneto-optical properties of nanostructured magnetic materials. In this paper, we shall describe a robust methodology recently developed by us that utilizes a dual PEM setup. As an example of its application, we report on the magneto-optical characteristics of focused Ga ion beam patterned Fe films. We have investigated Ga ion irradiation of single-layer polycrystalline Fe films deposited on Si3N4 substrates, which allows us to study the effects of ion implantation with minimum added complications. Complemented by structural and other characterization techniques, the absolute measurement of magneto-optical effects through the determination of Stokes parameters has enabled us to effectively separate the various contributions from film thinning due to sputtering, structural modifications and compositional changes caused by Ga incorporation. A comparison is also made between the magneto-optical behavior of patterned thin films and that of anodic aluminum oxide embedded magnetic nanowire arrays.

Temporal blastemal cell gene expression analysis in the kidney reveals new Wnt and related signaling pathway genes to be essential for Wilms' tumor onset.

Wilms' tumors (WTs) originate from metanephric blastema cells that are unable to complete differentiation, resulting in triphasic tumors composed of epithelial, stromal and blastemal cells, with the latter harboring molecular characteristics similar to those of the earliest kidney development stages. Precise regulation of Wnt and related signaling pathways has been shown to be crucial for correct kidney differentiation. In this study, the gene expression profile of Wnt and related pathways was assessed in laser-microdissected blastemal cells in WTs and differentiated kidneys, in human and in four temporal kidney differentiation stages (i.e. E15.5, E17.5, P1.5 and P7.5) in mice, using an orthologous cDNA microarray platform. A signaling pathway-based gene signature was shared between cells of WT and of earliest kidney differentiation stages, revealing genes involved in the interruption of blastemal cell differentiation in WT. Reverse transcription-quantitative PCR showed high robustness of the microarray data demonstrating 75 and 56% agreement in the initial and independent sample sets, respectively. The protein expression of CRABP2, IGF2, GRK7, TESK1, HDGF, WNT5B, FZD2 and TIMP3 was characterized in WTs and in a panel of human fetal kidneys displaying remarkable aspects of differentiation, which was recapitulated in the tumor. Taken together, this study reveals new genes candidate for triggering WT onset and for therapeutic treatment targets.

Patient experience and satisfaction with awake craniotomy for brain tumours.

Awake craniotomy is increasingly used to facilitate safe maximal resection of brain tumours. Very little published data is available to determine patient experiences and satisfaction. This knowledge may lead to improvement in technique and enhance future patient care. In 2006, we began to use conscious sedation ('full awake technique') for craniotomies for tumour resection. A questionnaire designed with reference to Royal College of Surgeons (RCS) guidelines was sent out to 60 consecutive patients. Four areas of care were explored. These included the out-patient consultation with the neurosurgeon, anaesthetic consultation, operation and the post-operative period. Fourty-five responses were received. Ninety-three percent of the patients in our study felt involved sufficiently in the decision for awake surgery and felt they were given enough information when seen in the surgical consultation. However, only 64% of patients received written information in advance of their surgical date. Ninety-one percent of patients were confident that they would be looked after during surgery following their anaesthetic consultation. Eighty-seven percent of patients felt at ease during surgery. Twenty-four percent experienced some discomfort during surgery, some of which was related to positioning of the patient rather than surgical technique. Fifty-six percent of our patients reported no post-operative pain. Eighty-four percent of patients were happy with timing of their discharge. Eighty percent felt well supported post-discharge. This study demonstrates high levels of patient satisfaction and provides surgeons with useful data for consenting patients. We identified no difference in levels of patient satisfaction comparing day-case patients with those admitted. We identified areas for improvement including provision of written information, enhancing post-discharge support and allowing more time for anaesthetic discussion before surgery.

Anthropomorphic measurements and event-free survival in patients with favorable histology Wilms tumor: a report from the Children's Oncology Group.

PURPOSE: We retrospectively examined the effect of body weight and body mass index (BMI) on event-free survival (EFS) of children with Wilms tumor treated on National Wilms Tumor Study-5 (NWTS-5). PATIENTS AND METHODS: Eligible study participants: stages I-IV favorable histology Wilms tumor with immediate nephrectomy; height and weight recorded at diagnosis, and loss of heterozygosity for chromosomes 1p and 16q assessed. RESULTS: A total of 1,532 patients were included in the analysis. The median follow-up was 4.9 years. 493 patients were less than 2 years of age and 1039 were 2 years of age or older. In both age groups there were more patients than expected with a weight or body mass index (BMI) less than the 10 per thousand or greater than the 90 per thousand. There was no relationship of weight-for-age or BMI-for-age and EFS in univariate analyses (P = 0.28, log-rank test for both comparisons). A Cox proportional hazards model, stratified by risk/treatment groups, showed that, among patients less than 2 years of age, low or high weight-for-age was not predictive of EFS (P = 0.16). Similarly, a Cox proportional hazards model, stratified by risk/treatment groups, showed that among patients greater than 2 years of age, low or high body mass index for age was not predictive of EFS (P = 0.58). CONCLUSIONS: There was no evidence that anthropomorphic data obtained at diagnosis for patients with favorable histology stages I-IV Wilms tumor was predictive for EFS in the setting of current treatment regimens. There were more patients with lower or higher weight/BMI than expected.

Day-case neurosurgery for brain tumours: the early United Kingdom experience.

Day-case biopsy and craniotomy for brain tumours have been reported as safe and feasible options for selected patients. The incidence and timing of complications after such procedures has also been characterized in recent publications. However, more widespread adoption of day-case cranial neurosurgery has not taken place. We report the first UK series of day-case surgery for intra-axial tumours, consisting of 30 image-guided biopsies and 11 craniotomies, taking place over 1 year from October 2006. Patients were studied prospectively and 27/30 biopsy and 9/11 craniotomy patients were discharged 6 h postoperatively. One biopsy case was admitted due to increased headache postoperatively, but with a normal CT and one craniotomy case had transient worsening of lower limb paresis requiring overnight admission. The three other overnight admissions were for patient preference. One biopsy patient was readmitted 30 h postoperatively with a seizure and discharged the following day. No patients suffered an adverse outcome. The results are presented together with the Toronto series of 284 cases over 11 years, also with no patients suffering an adverse outcome because of planned early discharge. These results suggest that day-case surgery for brain tumours is a safe and feasible option for patients in the UK.

Complex patterns of chromosome 9 alterations including the p16INK4a locus in Wilms tumours.

BACKGROUND: Previous data implicating genetic and epigenetic events on chromosome 9, including the CDKN2A/2B locus, as molecular predictors of Wilms tumour relapse, have been conflicting. AIMS: To clarify this using genome-wide and focused molecular genetic analysis. METHODS: Microarray-based comparative genomic hybridisation (aCGH) using genome-wide coverage was applied to 76 favourable histology Wilms tumours. Additional investigation of the 9p21 locus was carried out using loss of heterozygosity (LOH) and fluorescence in situ hybridisation (FISH), as well as immunohistochemistry for CDKN2A/p16(INK4a) on a paediatric renal tumour tissue microarray. RESULTS: Approximately half of the tumours were found to show chromosome 9 copy number changes. Those cases which harboured alterations comprised at least four distinct patterns: gain of the entire chromosome, loss of 9p, gain of 9q34, or a more complex combination of gains/losses. None of these tumour groups showed any statistically significant correlation with clinicopathological variables. Deletion mapping of 9p by LOH revealed several regions of overlap, including the CDKN2A/2B locus in 4/34 (11.8%) tumours, which was confirmed to represent hemizygous deletions by FISH. CDKN2A/p16(INK4a) protein expression was predominantly negative in Wilms tumours as assessed by immunohistochemistry on a tissue array, reflecting the expression pattern in normal kidney. However, 38/236 (16.1%) non-anaplastic Wilms tumours, 4/9 (44.4%) anaplastic Wilms tumours, 5/7 (71.4%) rhabdoid tumours of the kidney, and 4/10 (40%) clear cell sarcomas of the kidney showed nuclear CDKN2A/p16(INK4a )immunoreactivity. CONCLUSIONS: These data reveal the complex nature of genetic alterations on chromosome 9 in Wilms tumours, but do not provide evidence for their involvement in or association with treatment failure.

Molecular profiling of isolated histological components of Wilms tumor implicates a commom role for the Wnt signaling pathway in kidney and tumor development

Wilms tumor (WT), a tumor composed of three histological components - blastema (BL), epithelia and stroma - is considered an appropriate model system to study the biological relationship between differentiation and tumorigenesis. To investigate molecular associations between nephrogenesis and WT, the gene expression pattern of individual cellular components was analyzed, using a customized platform containing 4,608 genes. WT gene expression patterns were compared to genes regulated during kidney differentiation. BL had a closer gene expression pattern to the earliest stage of normal renal development. The BL gene expression pattern was compared to that of fetal kidney (FK) and also between FK and mature kidney, identifying 25 common deregulated genes supposedly involved in the earliest events of WT onset. Quantitative RT-PCR was performed, confirming the difference in expression levels for 13 of 16 genes (81.2%) in the initial set and 8 of 13 (61.5%) in an independent set of samples. An overrepresentation of genes belonging to the Wnt signaling pathway was identified, namely PLCG2, ROCK2 and adenomatous polyposis coli (APC). Activation of the Wnt pathway was confirmed in WT, using APC at protein level and PLCG2 at mRNA and protein level. APC showed positive nuclear immunostaining for an independent set of WT samples, similarly to the FK in week 11. Lack of PLCG2 expression was confirmed in WT and in FK until week 18. Taken together, these results provided molecular evidence of the recapitulation of the embryonic kidney by WT as well as involvement of the Wnt pathway in the earliest events of WT onset.

C1584 in von Willebrand factor is necessary for enhanced proteolysis by ADAMTS13 in vitro.

The cysteine variant of the amino acid change tyrosine/cysteine 1584 (Y/C1584) in von Willebrand factor (VWF) has previously been shown to cosegregate with increased susceptibility of VWF to proteolysis by ADAMTS13. It is not known whether C1584 itself confers increased proteolysis or is linked to a causative change elsewhere in VWF. To address whether C1584 underlies enhanced susceptibility of VWF to ADAMTS13-mediated proteolysis, a single family comprising two heterozygous Y/C1584 individuals and four homozygous Y/Y1584 individuals was investigated. The essential regions of the VWF gene were sequenced in all six individuals and ADAMTS13-mediated proteolysis of plasma VWF was assessed for each individual. Comparison of the VWF coding sequences for the Y/C1584 individuals with those for the Y/Y1584 individuals revealed that two amino acid variants were unique to the heterozygotes: R484 and C1584. The plasma VWF of the two heterozygotes showed increased susceptibility to proteolysis in vitro compared with that of the four homozygotes. In the present study we demonstrate that R484, in the absence of C1584, does not influence VWF proteolysis. Enhanced proteolysis occurred only in the presence of Cys1584. Thus, Cys1584 is necessary for increased susceptibility of VWF to proteolysis by ADAMTS13.

Utilizing the assassin bug, Pristhesancus plagipennis (Hemiptera: Reduviidae), as a biological control agent within an integrated pest management programme for Helicoverpa spp. (Lepidoptera: Noctuidae) and Creontiades spp. (Hemiptera: Miridae) in cotton.

Helicoverpa spp. and mirids, Creontiades spp., have been difficult to control biologically in cotton due to their unpredictable temporal abundance combined with a cropping environment often made hostile by frequent usage of broad spectrum insecticides. To address this problem, a range of new generation insecticides registered for use in cotton were tested for compatibility with the assassin bug, Pristhesancus plagipennis (Walker), a potential biological control agent for Helicoverpa spp. and Creontiades spp. Indoxacarb, pyriproxifen, buprofezin, spinosad and fipronil were found to be of low to moderate toxicity on P. plagipennis whilst emamectin benzoate, abamectin, diafenthiuron, imidacloprid and omethaote were moderate to highly toxic. Inundative releases of P. plagipennis integrated with insecticides identified as being of low toxicity were then tested and compared with treatments of P. plagipennis and the compatible insecticides used alone, conventionally sprayed usage practice and an untreated control during two field experiments in cotton. The biological control provided by P. plagipennis nymphs when combined with compatible insecticides provided significant (P<0.001) reductions in Helicoverpa and Creontiades spp. on cotton and provided equivalent yields to conventionally sprayed cotton with half of the synthetic insecticide input. Despite this, the utilization of P. plagipennis in cotton as part of an integrated pest management programme remains unlikely due to high inundative release costs relative to other control technologies such as insecticides and transgenic (Bt) cotton varieties.

Analysis by array CGH of genomic changes associated with the progression or relapse of Wilms' tumour.

Despite aggressive salvage regimens, approximately half of all children who suffer a Wilms' tumour recurrence will die of their disease. Although there are increasing data on molecular genetic prognostic factors present in the tumour at diagnosis, there is little information regarding the molecular events that occur with Wilms' tumour progression and relapse. In the present study, microarray-based comparative genomic hybridization (aCGH) analysis has been carried out on 58 Wilms' tumour samples, which included 38 untreated primary and 20 recurrent tumours. A higher degree of copy number changes was observed in the recurrent tumours (33.0% genomic clones) than in the primary tumour (21.2%). Paired analysis highlighted the acquisition of 15q gain with high levels of IGF1R expression in the tumour recurrence in two cases. The most statistically significant abnormality acquired between diagnosis and relapse was loss of 17p. One case that experienced 17p loss was classified as favourable histology at diagnosis, but exhibited diffuse anaplasia at recurrence and had a homozygous TP53 deletion. Another instructive case with a constitutional 11p13 deletion presented with bilateral tumours and suffered two subsequent recurrences in the left kidney. A somatic WT1 mutation was found only in the right kidney tumour, while the constitutional 11p13 deletion was the only abnormality detected in the initial left kidney tumour by aCGH. The two subsequent relapses in the left kidney contained an accumulation of additional genetic alterations, including an independent WT1 mutation.

Array CGH profiling of favourable histology Wilms tumours reveals novel gains and losses associated with relapse.

Despite the excellent survival of Wilms tumour patients treated with multimodality therapy, approximately 15% will suffer from tumour relapse, where response rates are markedly reduced. We have carried out microarray-based comparative genomic hybridisation on a series of 76 Wilms tumour samples, enriched for cases which recurred, to identify changes in DNA copy number associated with clinical outcome. Using 1Mb-spaced genome-wide BAC arrays, the most significantly different genomic changes between favourable histology tumours that did (n = 37), and did not (n = 39), subsequently relapse were gains on 1q, and novel deletions at 12q24 and 18q21. Further relapse-associated loci included losses at 1q32.1, 2q36.3-2q37.1, and gain at 13q31. 1q gains correlated strongly with loss of 1p and/or 16q. In 3 of 11 cases with concurrent 1p(-)/1q(+), a breakpoint was identified at 1p13. Multiple low-level sub-megabase gains along the length of 1q were identified using chromosome 1 tiling-path arrays. One such recurrent region at 1q22-q23.1 included candidate genes RAB25, NES, CRABP2, HDGF and NTRK1, which were screened for mRNA expression using quantitative RT-PCR. These data provide a high-resolution catalogue of genomic copy number changes in relapsing favourable histology Wilms tumours.

Multiple gangliogliomas of the optic pathway.

We report a case of multiple gangliogliomas of the optic pathway in an 18-year-old boy. He presented with visual disturbance mainly in his left eye, non-specific headaches, and episodes of sensory disturbance in his left arm. Visual acuity was 6/9 and 6/24 in his right and left eye respectively. He did not have any Lisch nodules. Optic atrophy was noted in his left eye. MRI scan revealed multiple enhancing lesions involving the optic chiasm, left optic tract, right lateral geniculate body, and right optic radiation in the temporal lobe. Stereotactic biopsy of the temporal tumour confirmed ganglioglioma. Multiple gangliogliomas of the optic pathway has not been hitherto described.

Evaluating legume species as alternative trap crops to chickpea for management of Helicoverpa spp. (Lepidoptera: Noctuidae) in central Queensland cotton cropping systems.

Mounting levels of insecticide resistance within Australian Helicoverpa spp. populations have resulted in the adoption of non-chemical IPM control practices such as trap cropping with chickpea, Cicer arietinum (L.). However, a new leaf blight disease affecting chickpea in Australia has the potential to limit its use as a trap crop. Therefore this paper evaluates the potential of a variety of winter-active legume crops for use as an alternative spring trap crop to chickpea as part of an effort to improve the area-wide management strategy for Helicoverpa spp. in central Queensland's cotton production region. The densities of Helicoverpa eggs and larvae were compared over three seasons on replicated plantings of chickpea, Cicer arietinum (L.), field pea Pisum sativum (L), vetch, Vicia sativa (L.) and faba bean, Vicia faba (L.). Of these treatments, field pea was found to harbour the highest densities of eggs. A partial life table study of the fate of eggs oviposited on field pea and chickpea suggested that large proportions of the eggs laid on field pea suffered mortality due to dislodgment from the plants after oviposition. Plantings of field pea as a replacement trap crop for chickpea under commercial conditions confirmed the high level of attractiveness of this crop to ovipositing moths. The use of field pea as a trap crop as part of an area-wide management programme for Helicoverpa spp. is discussed.

Treatment with nephrectomy only for small, stage I/favorable histology Wilms' tumor: a report from the National Wilms' Tumor Study Group.

PURPOSE: Children younger than 24 months with small (< 550 g), favorable histology (FH) Wilms tumors (WTs) were shown in a pilot study to have an excellent prognosis when treated with nephrectomy only. PATIENTS AND METHODS: A study of nephrectomy only for the treatment of selected children with FH WT was undertaken. Stringent stopping rules were designed to insure closure of the study if the true 2-year relapse-free survival rate was 90% or lower. RESULTS: Seventy-five previously untreated children younger than 24 months with stage I/FH WTs for which the surgical specimen weighed less than 550 g were treated with nephrectomy only. Three patients developed metachronous, contralateral WT 1.1, 1.4, and 2.3 years after nephrectomy, and eight patients relapsed 0.3 to 1.05 years after diagnosis (median, 0.4 years; mean, 0.51 years). The sites of relapse were lung (n = 5) and operative bed (n = 3). The 2-year disease-free (relapse and metachronous contralateral WT) survival rate was 86.5%. The 2-year survival rate is 100% with a median follow-up of 2.84 years. The 2-year disease-free survival rate (excluding metachronous contralateral WT) was 89.2%, and the 2-year cumulative risk of metachronous contralateral WT was 3.1%. CONCLUSION: Children younger than 24 months treated with nephrectomy only for a stage I/FH WT that weighed less than 550 g had a risk of relapse, including the development of metachronous contralateral WT, of 13.5% 2 years after diagnosis. All patients who experienced relapse on this trial are alive at this time. This approach will be re-evaluated in a clinical trial using a less conservative stopping rule.

Glucocorticoids modulate the NGF mRNA response in the rat hippocampus after traumatic brain injury.

Nerve growth factor (NGF) expression in the rat hippocampus is increased after experimental traumatic brain injury (TBI) and is neuroprotective. Glucocorticoids are regulators of brain neurotrophin levels and are often prescribed following TBI. The effect of adrenalectomy (ADX) and corticosterone (CORT) replacement on the expression of NGF mRNA in the hippocampus after TBI has not been investigated to date. We used fluid percussion injury and in situ hybridisation to evaluate the expression of NGF mRNA in the hippocampus 4 h after TBI in adrenal-intact or adrenalectomised rats (with or without CORT replacement). TBI increased expression of NGF mRNA in sham-ADX rats, but not in ADX rats. Furthermore, CORT replacement in ADX rats restored the increase in NGF mRNA induced by TBI. These findings suggest that glucocorticoids have an important role in the induction of hippocampal NGF mRNA after TBI.

Gain of 1q is associated with adverse outcome in favorable histology Wilms' tumors.

Although several genes/genetic loci involved in the etiology of Wilms' tumor have been identified, little is known of the molecular changes associated with relapse. We therefore undertook an analysis by comparative genomic hybridization (CGH) of 58 tumor samples of favorable histology Wilms' tumor taken at initial diagnosis and/or relapse. Tumors with anaplastic histology were excluded as this is known to be associated with p53 mutation and a poor prognosis. A control group of 21 Wilms' tumors that did not relapse was also analyzed. The overall frequency of gains or losses of genetic material detected by CGH was similar in both groups (77% in relapsing tumors and 70% in the nonrelapse group) as was the median number of changes per tumor (relapse group: n = 4, range, 1 to 19; nonrelapse group: n = 3, range, 1 to 8). However, gain of 1q was significantly more frequent in the relapse series [27 of 46 (59%) versus 5 of 21 (24%), P: = 0.019]. In 12 matched tumor pairs, the CGH profiles, including 1q gain, were similar at diagnosis and relapse, with little evidence for further copy number changes being involved in clonal evolution. The results suggest that 1q gain at diagnosis could be used to identify patients with favorable histology Wilms' tumor at increased risk of relapse who might benefit from early treatment intensification.

The survivin:fas ratio in pediatric renal tumors.

BACKGROUND/PURPOSE: Apoptosis factors inducing or preventing cell death may govern the behavior of certain tumors. Fas is a pro-apoptotic receptor that induces cell death when bound by its ligand and is expressed at greater levels in pediatric renal tumors of good prognosis. Survivin is a novel inhibitor of apoptosis that is expressed in a cell cycle-dependent manner and is abundantly expressed in several tumors of unfavorable histology. This study evaluates the expression of survivin, as well as the prognostic value of the survivin:fas ratio in various types and stages of pediatric renal tumors. METHODS: Multiple apoptosis mRNA species were quantified by Rnase protection assay (RPA) in 32 pediatric renal tumors and adjacent normal kidney specimens before chemotherapy: Wilms' tumor (WT), n = 9; clear cell sarcoma (CCS), n = 4; rhabdoid tumor of the kidney (RTK), n = 5; mesoblastic nephroma (MN), n = 3 and normal kidney, n = 11. Western Blot and immunocytochemistry were used to confirm survivin protein expression in a selective specimen survey. Follow-up data were obtained on patient outcomes, and antiapoptotic to proapoptotic ratios were calculated and correlated with clinical recurrence of disease. RESULTS: Pediatric renal tumors express greater levels of both pro- and antiapoptotic factors than normal kidney. Survivin and fas appeared to be expressed differentially in the tumor specimens sampled. Five of 10 (50%) tumors that went on to recur expressed survivin, whereas survivin was present in only 2 of 11 (18%) nonrecurrent tumors. Conversely, only 2 of 10 (20%) tumors that recurred were fas positive, whereas 5 of 11 (45%) tumors that did not recur expressed fas. The mean survivin:fas ratio was significantly greater in the 10 tumors that went on to recur after treatment (4 RTK, 3 CCS, 3 WT), than in tumors not recurring (2.16+/-1.4 v 1.0+/-1.07; P =.01, Kruskal-Wallis test). The positive predictive value of tumor recurrence was 85.7% (CI: 42.1%, 99.6%) and the negative predictive value was 71.4% (CI: 41.9%, 91.6%) when a cutoff ratio of 1.6 was considered. CONCLUSIONS: The survivin:fas mRNA ratio is of prognostic value in its ability to predict recurrent disease in children undergoing treatment for pediatric renal tumors. In this series, a ratio of greater than 1.6 predicted recurrent disease with a high probability irrespective of clinical stage or pathologic type. Determining the survivin:fas ratio may guide treatment, follow-up and counseling of patients with pediatric renal tumors.