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1.  Clear Cell Sarcoma of the Kidney Demonstrates an Embryonic Signature Indicative of a Primitive Nephrogenic Origin 
Genes, chromosomes & cancer  2014;53(5):381-391.
Clear cell sarcoma of the kidney (CCSK) is a tumor affecting children with a median age of 3 years at diagnosis. The cell of origin of CCSK is unknown and data on the molecular changes giving rise to CCSK is scarce. This has hindered the identification of positive diagnostic markers and development of molecularly targeted treatment protocols for CCSK. We have characterized a panel of CCSK to gain information regarding its molecular profile and possible origin. High-resolution genomic analysis with single nucleotide polymorphism array of 37 tumors did not reveal any clues to the mechanisms behind tumor development as remarkably few genetic imbalances were found. Gene expression analysis revealed a highly characteristic gene signature, enriched for pathways involved in embryonic development, including kidney formation. The presence of markers for two different developmental lineages in the embryonic kidney was therefore investigated in the tumor cells. FOXD1 which identifies cells giving rise to stromal elements, and CITED1, a marker for cells primed for nephrogenic epithelial differentiation, were both highly expressed in CCSK. In addition, the early embryonic marker OSR1 was expressed at higher levels in CCSK than in Wilms tumor, normal fetal kidney or adult kidney. As this marker discriminates the intermediate mesoderm from other mesodermal structures, our study could suggest that CCSK arises from a mesodermal cell type that retains the capacity to initiate differentiation towards both nephrons and stroma, but remains locked in a primitive state.
doi:10.1002/gcc.22149
PMCID: PMC4334316  PMID: 24488803
2.  Inter-rater reliability of surgical reviews for AREN03B2: A COG renal tumor committee study✩ 
Journal of pediatric surgery  2013;49(1):154-158.
Purpose
The Children's Oncology Group (COG) renal tumor study (AREN03B2) requires real-time central review of radiology, pathology, and the surgical procedure to determine appropriate risk-based therapy. The purpose of this study was to determine the inter-rater reliability of the surgical reviews.
Methods
Of the first 3200 enrolled AREN03B2 patients, a sample of 100 enriched for blood vessel involvement, spill, rupture, and lymph node involvement was selected for analysis. The surgical assessment was then performed independently by two blinded surgical reviewers and compared to the original assessment, which had been completed by another of the committee surgeons. Variables assessed included surgeon-determined local tumor stage, overall disease stage, type of renal procedure performed, presence of tumor rupture, occurrence of intraoperative tumor spill, blood vessel involvement, presence of peritoneal implants, and interpretation of residual disease. Inter-rater reliability was measured using the Fleiss' Kappa statistic two-sided hypothesis tests (Kappa, p-value).
Results
Local tumor stage correlated in all 3 reviews except in one case (Kappa = 0.9775, p < 0.001). Similarly, overall disease stage had excellent correlation (0.9422, p < 0.001). There was strong correlation for type of renal procedure (0.8357, p < 0.001), presence of tumor rupture (0.6858, p < 0.001), intraoperative tumor spill (0.6493, p < 0.001), and blood vessel involvement (0.6470, p < 0.001). Variables that had lower correlation were determination of the presence of peritoneal implants (0.2753, p < 0.001) and interpretation of residual disease status (0.5310, p < 0.001).
Conclusion
The inter-rater reliability of the surgical review is high based on the great consistency in the 3 independent review results. This analysis provides validation and establishes precedent for real-time central surgical review to determine treatment assignment in a risk-based stratagem for multimodal cancer therapy.
doi:10.1016/j.jpedsurg.2013.09.047
PMCID: PMC4076163  PMID: 24439601
Wilms Tumor; Quality assurance; Surgery; Outcomes
3.  Children’s Oncology Group’s 2013 Blueprint for Research: Renal Tumors 
Pediatric blood & cancer  2012;60(6):994-1000.
Renal malignancies are among the most prevalent pediatric cancers. The most common is favorable histology Wilms tumor (FHWT), which has 5-year overall survival exceeding 90%. Other pediatric renal malignancies, including anaplastic Wilms tumor, clear cell sarcoma, malignant rhabdoid tumor, and renal cell carcinoma, have less favorable outcomes. Recent clinical trials have identified gain of chromosome 1q as a prognostic marker for FHWT. Upcoming studies will evaluate therapy adjustments based on this and other novel biomarkers. For high-risk renal tumors, new treatment regimens will incorporate biological therapies. A research blueprint, viewed from the perspective of the Children’s Oncology Group, is presented.
doi:10.1002/pbc.24419
PMCID: PMC4127041  PMID: 23255438
Wilms tumor; renal cell carcinoma; malignant rhabdoid tumor; clear cell sarcoma
4.  Mentoring in Pediatric Oncology: A Report from the Children’s Oncology Group Young Investigator Committee 
Journal of pediatric hematology/oncology  2013;35(6):10.1097/MPH.0b013e31829eec33.
A formal Mentorship Program within the Children’s Oncology Group (COG) was established to pair young investigators (mentees) with established COG members (mentors). Despite the AAP policy statement promoting mentorship programs, there are no publications describing and evaluating national mentorship programs in pediatric subspecialties. In this study, a series of internal program evaluations were performed using surveys of both mentors and mentees. Responses were de-identified and analyzed to determine the utility of the program by both participant satisfaction and self-reported academic productivity. Results indicated that mentees were generally satisfied with the program. Mentor-mentee pairs that met at least quarterly demonstrated greater academic productivity than pairings that met less frequently. This formal mentorship program appeared to have subjective and objective utility for the development of academic pediatric subspecialists.
doi:10.1097/MPH.0b013e31829eec33
PMCID: PMC3839621  PMID: 23892351
mentorship; pediatric oncology
5.  miRNA Expression Profiling Enables Risk Stratification in Archived and Fresh Neuroblastoma Tumor Samples 
Purpose
More accurate assessment of prognosis is important to further improve the choice of risk-related therapy in neuroblastoma (NB) patients. In this study, we aimed to establish and validate a prognostic miRNA signature for children with NB and tested it in both fresh frozen and archived formalin-fixed paraffin-embedded (FFPE) samples.
Experimental Design
Four hundred-thirty human mature miRNAs were profiled in two patient subgroups with maximally divergent clinical courses. Univariate logistic regression analysis was used to select miRNAs correlating with NB patient survival. A 25-miRNA gene signature was built using 51 training samples, tested on 179 test samples, and validated on an independent set of 304 fresh frozen tumor samples and 75 archived FFPE samples.
Results
The 25-miRNA signature significantly discriminates the test patients with respect to progression-free and overall survival (P < 0.0001), both in the overall population and in the cohort of high-risk patients. Multivariate analysis indicates that the miRNA signature is an independent predictor of patient survival after controlling for current risk factors. The results were confirmed in an external validation set. In contrast to a previously published mRNA classifier, the 25-miRNA signature was found to be predictive for patient survival in a set of 75 FFPE neuroblastoma samples.
Conclusions
In this study, we present the largest NB miRNA expression study so far, including more than 500 NB patients. We established and validated a robust miRNA classifier, able to identify a cohort of high-risk NB patients at greater risk for adverse outcome using both fresh frozen and archived material.
doi:10.1158/1078-0432.CCR-11-0610
PMCID: PMC4008338  PMID: 22031095
6.  Peripheral Neuroblastic Tumors with Genotype-Phenotype Discordance: A Report from the Children’s Oncology Groupand the International Neuroblastoma Pathology Committee 
Pediatric blood & cancer  2012;60(3):363-370.
Background
Of 4,706 peripheral neuroblastic tumors (pNTs) registered on the Children’s Cancer Group and Children’s Oncology Group Neuroblastoma Study between 1989 and 2010, 51 cases (1.1%) had genotype-phenotype discordance characterized by MYCN amplification (indicating poor prognosis) and Favorable Histology (indicating better prognosis).
Procedure
To distinguish prognostic subgroups in the genotype-phenotype discordant pNTs, two subgroups, “conventional” and “bull’s eye”, were identified based on the nuclear morphology. The “conventional” tumors (35 cases) included: Neuroblastoma, Poorly differentiated subtype (NB-PD, 26 cases) with “salt-and-pepper” nuclei; Neuroblastoma, Differentiating subtype (4 cases); Ganglioneuroblastoma, Intermixed (3 cases); and Ganglioneuroma, Maturing subtype (2 cases). The “bull’s eye” tumors included NB-PD with prominent nucleoli (16 cases). Clinicopathologic characteristics of these two subgroups were analyzed. N-myc protein expression was tested immunohistochemically on available tumors.
Results
No significant difference was found between these two subgroups in the distribution of prognostic factors such as age at diagnosis, clinical stage, histopathology category/subtype, mitosis-karyorrhexis index, ploidy, 1p LOH, and unbalanced 11qLOH. However, prognosis of the patients with “conventional” tumors (5-year EFS 85.7±12.2%; OS 89.3±10.3%) was significantly better than those with “bull’s eye” tumors (EFS 31.3±13.0%; OS 42.9±16.2%) (P=0.0010 and 0.0008, respectively). Immunohistochemically all (11/11) tested “conventional” tumors were negative, and 10/11 tested “bull’s eye” tumors were positive for N-myc protein expression.
Conclusions
Based on the presence or absence of prominent nucleoli (the putative site of RNA synthesis/accumulation leading to N-myc protein expression), two prognostic subgroups, “conventional” with a better prognosis and “bull’s eye” with a poor prognosis, were distinguished among the genotype-phenotype discordant pNTs.
doi:10.1002/pbc.24238
PMCID: PMC3397468  PMID: 22744966
neuroblastoma; International Neuroblastoma Pathology Classification; MYCN; genotype-phenotype correlation; prognosis; immunohistochemistry
7.  A Pilot Study of Tandem High Dose Chemotherapy with Stem Cell Rescue as Consolidation for High Risk Neuroblastoma: Children’s Oncology Group study ANBL00P1 
Bone marrow transplantation  2013;48(7):947-952.
Increasing treatment intensity has improved outcomes for children with neuroblastoma. We performed a pilot study in the Children’s Oncology Group (COG) to assess feasibility and toxicity of a tandem myeloablative regimen without total body irradiation (TBI) supported by autologous CD34 selected peripheral blood stem cells. Forty-one patients with high-risk neuroblastoma were enrolled; eight patients did not receive any myeloablative consolidation procedure, and seven received only one. Two patients out of 41 (4.9%) experienced transplant-related mortality. CD34 selection was discontinued after subjects were enrolled due to serious viral illness. From the time of study enrollment, the overall 3-year event-free survival (EFS) and overall survival (OS) were 44.8±9.6% and 59.2±9.2% (N=41). These results demonstrate that tandem transplantation in the cooperative group setting is feasible and support a randomized comparison of single versus tandem myeloablative consolidation with PBSC support for high-risk neuroblastoma.
doi:10.1038/bmt.2012.276
PMCID: PMC3638062  PMID: 23334272
pediatric; neuroblastoma; tandem transplant; hematopoietic stem cell transplant
8.  Truncated DNMT3B isoform DNMT3B7 suppresses growth, induces differentiation, and alters DNA methylation in human neuroblastoma 
Cancer research  2012;72(18):4714-4723.
Epigenetic changes in pediatric neuroblastoma may contribute to the aggressive pathophysiology of this disease, but little is known about the basis for such changes. In this study, we examined a role for the DNA methyltransferase DNMT3B, in particular, the truncated isoform DNMT3B7 which is generated frequently in cancer. To investigate if aberrant DNMT3B transcripts alter DNA methylation, gene expression, and phenotypic character in neuroblastoma, we measured DNMT3B expression in primary tumors. Higher levels of DNMT3B7 were detected in differentiated ganglioneuroblastomas compared to undifferentiated neuroblastomas, suggesting that expression of DNMT3B7 may induce a less aggressive clinical phenotype. To test this hypothesis, we investigated the effects of enforced DNMT3B7 expression in neuroblastoma cells, finding a significant inhibition of cell proliferation in vitro and angiogenesis and tumor growth in vivo. DNMT3B7-positive cells had higher levels of total genomic methylation and a dramatic decrease in expression of the FOS and JUN family members that comprise AP1 transcription factors. Consistent with an established antagonistic relationship between AP1 expression and retinoic acid receptor activity, increased differentiation was seen in the DNMT3B7-expressing neuroblastoma cells following treatment with all-trans retinoic acid (ATRA) compared to controls. Our results indicate that DNMT3B7 modifies the epigenome in neuroblastoma cells to induce changes in gene expression, inhibit tumor growth, and increase sensitivity to ATRA.
doi:10.1158/0008-5472.CAN-12-0886
PMCID: PMC3445765  PMID: 22815530
DNMT3B; Neuroblastoma; DNA Methylation
9.  A genome-wide association study identifies susceptibility loci for Wilms tumor 
Nature genetics  2012;44(6):681-684.
Wilms tumor is the most common renal malignancy of childhood. To identify common variants that confer susceptibility to Wilms tumor we conducted a genome-wide association study in 757 cases and 1,879 controls. We evaluated ten SNPs in regions significant at P<5×10−5 in two independent replication series from the UK (769 cases and 2,814 controls) and the US (719 cases and 1,037 controls). We identified clear significant associations at two loci, 2p24 (rs3755132, P=1.03×10−14 and rs807624, P=1.32×10−14) and 11q14 (rs790356, P=4.25 ×10−15). Both regions contain genes that are plausibly related to Wilms tumorigenesis. We also identified candidate signals at 5q14, 22q12 and Xp22.
doi:10.1038/ng.2251
PMCID: PMC3400150  PMID: 22544364
10.  Pilot Induction Regimen Incorporating Pharmacokinetically Guided Topotecan for Treatment of Newly Diagnosed High-Risk Neuroblastoma: A Children's Oncology Group Study 
Journal of Clinical Oncology  2011;29(33):4351-4357.
Purpose
To assess the feasibility of adding dose-intensive topotecan and cyclophosphamide to induction therapy for newly diagnosed high-risk neuroblastoma (HRNB).
Patients and Methods
Enrolled patients received two cycles of topotecan (approximately 1.2 mg/m2/d) and cyclophosphamide (400 mg/m2/d) for 5 days followed by four cycles of multiagent chemotherapy (Memorial Sloan-Kettering Cancer Center [MSKCC] regimen). Pharmacokinetically guided topotecan dosing (target systemic exposure with area under the curve of 50 to 70 ng/mL/hr) was performed. Peripheral-blood stem cell (PBSC) harvest and surgical resection of residual primary tumor occurred after cycles 2 and 5, respectively. Patients achieving at least a partial response received myeloablative chemotherapy with PBSC rescue and radiation to the presurgical primary tumor volume. Oral 13-cis-retinoic acid maintenance therapy was administered twice daily for 14 days in six 28-day cycles.
Results
Thirty-one patients were enrolled onto the study. No deaths related to toxicity or dose-limiting toxicities occurred during induction. Mucositis rarely occurred after topotecan cycles (9.7%) in contrast to 30% after MSKCC cycles. Thirty patients underwent PBSC collection with median 31.1 × 106 CD34+ cells/kg (range, 1.8 to 541.8 × 106 CD34+ cells/kg), all negative for tumor contamination by immunocytochemical analysis. Targeted topotecan systemic exposure was achieved in 26 (84%) of 31 patients. At the end of induction, 26 patients (84%) had tumor response and one patient had progressive disease. In the overall cohort, 3-year event-free and overall survival were 37.8% ± 9.4% and 57.1% ± 9.4%, respectively.
Conclusion
This pilot induction regimen was well tolerated with expected and reversible toxicities. These data support investigation of efficacy in a phase III clinical trial for newly diagnosed HRNB.
doi:10.1200/JCO.2010.34.3293
PMCID: PMC3221519  PMID: 22010014
11.  Phase II study of oral capsular 4-hydroxyphenylretinamide (4-HPR/fenretinide) in pediatric patients with refractory or recurrent neuroblastoma: A report from the Children’s Oncology Group NSC #374551; IND# 40294 
Purpose
To determine the response rate to oral capsular fenretinide in children with recurrent or biopsy proven refractory high-risk neuroblastoma.
Experimental Design
Patients received 7 days of fenretinide: 2475 mg/m2/day divided TID (<18 years) or 1800 mg/m2/day divided BID (≥18 years) every 21 days for a maximum of 30 courses. Patients with stable or responding disease after course 30 could request additional compassionate courses. Best response by course 8 was evaluated in Stratum 1 (measurable disease on CT/MRI +/− bone marrow and/or MIBG avid sites) and Stratum 2 (bone marrow and/or MIBG avid sites only).
Results
Sixty-two eligible patients, median age 5 years (range 0.6–19.9), were treated in Stratum 1 (n=38) and Stratum 2 (n=24). One partial response (PR) was seen in Stratum 2 (n=24 evaluable). No responses were seen in Stratum 1 (n=35 evaluable). Prolonged stable disease (SD) was seen in 7 patients in Stratum 1 and 6 patients in Stratum 2 for 4–45+ (median 15) courses. Median time to progression was 40 days (range 17–506) for Stratum 1 and 48 days (range 17–892) for Stratum 2. Mean 4-HPR steady state trough plasma concentrations were 7.25 µM (coefficient of variation 40–56%) at day 7 course 1. Toxicities were mild and reversible.
Conclusions
Although neither stratum met protocol criteria for efficacy, 1 PR + 13 prolonged SD occurred in 14/59 (24%) of evaluable patients. Low bioavailability may have limited fenretinide activity. Novel fenretinide formulations with improved bioavailability are currently in pediatric Phase I studies.
doi:10.1158/1078-0432.CCR-11-0995
PMCID: PMC3207022  PMID: 21908574
fenretinide; neuroblastoma; Phase II; ANBL0321
12.  Evaluation of Norepinephrine Transporter Expression and Metaiodobenzylguanidine Avidity in Neuroblastoma: A Report from the Children's Oncology Group 
Purpose. 123I-metaiodobenzylguanidine (MIBG) is used for the diagnostic evaluation of neuroblastoma. We evaluated the relationship between norepinephrine transporter (NET) expression and clinical MIBG uptake. Methods. Quantitative reverse transcription PCR (N = 82) and immunohistochemistry (IHC; N = 61) were performed for neuroblastoma NET mRNA and protein expression and correlated with MIBG avidity on diagnostic scans. The correlation of NET expression with clinical features was also performed. Results. Median NET mRNA expression level for the 19 MIBG avid patients was 12.9% (range 1.6–73.7%) versus 5.9% (range 0.6–110.0%) for the 8 nonavid patients (P = 0.31). Median percent NET protein expression was 50% (range 0–100%) in MIBG avid patients compared to 10% (range 0–80%) in nonavid patients (P = 0.027). MYCN amplified tumors had lower NET protein expression compared to nonamplified tumors (10% versus 50%; P = 0.0002). Conclusions. NET protein expression in neuroblastoma correlates with MIBG avidity. MYCN amplified tumors have lower NET protein expression.
doi:10.1155/2012/250834
PMCID: PMC3463166  PMID: 23050139
13.  CASZ1b, the Short Isoform of CASZ1 Gene, Coexpresses with CASZ1a during Neurogenesis and Suppresses Neuroblastoma Cell Growth 
PLoS ONE  2011;6(4):e18557.
In Drosophila, the CASZ1 (castor) gene encodes a zinc finger transcription factor and is a neural fate-determination gene. In mammals, the CASZ1 gene encodes two major isoforms, CASZ1a with 11 zinc fingers and CASZ1b with 5 zinc fingers. CASZ1b is more evolutionally conserved since it is the only homologue found in drosophila and Xenopus. Our previous study showed that full length CASZ1 (CASZ1a) functions to suppress growth in neuroblastoma tumor. However, the function of CASZ1b isoform in mammals is unknown. In this study, realtime PCR analyses indicate that mouse CASZ1b (mCASZ1b) is dynamically expressed during neurogenesis. CASZ1b and CASZ1a co-exist in all the neuronal tissues but exhibit distinct expression patterns spatially and temporally during brain development. CASZ1b and CASZ1a expression is coordinately upregulated by the differentiation agent Retinoic Acid, as well as agents that modify the epigenome in neural crest derived neuroblastoma cell lines. In contrast CASZ1b is down regulated while CASZ1a is upregulated by agents that raise intracellular cAMP levels. CASZ1b and CASZ1a have no synergistic or antagonistic activities on the regulation of their target NGFR gene transcription. Specific restoration of CASZ1b in NB cells suppresses tumor growth in vitro and in vivo. Consistent with its function role, we find that low CASZ1b expression is significantly associated with decreased survival probability of neuroblastoma patients (p<0.02). This study indicates that although their mechanisms of regulation may be distinct, both CASZ1b and CASZ1a have largely redundant but critical roles in suppressing tumor cell growth.
doi:10.1371/journal.pone.0018557
PMCID: PMC3072398  PMID: 21490919
14.  Outcome Prediction of Children with Neuroblastoma using a Multigene Expression Signature, a Retrospective SIOPEN/COG/GPOH Study 
The lancet oncology  2009;10(7):663-671.
BACKGROUND
More accurate prognostic assessment of patients with neuroblastoma is required to improve the choice of risk-related therapy. The aim of this study is to develop and validate a gene expression signature for improved outcome prediction.
METHODS
Fifty-nine genes were carefully selected based on an innovative data-mining strategy and profiled in the largest neuroblastoma patient series (n=579) to date using RT-qPCR starting from only 20 ng of RNA. A multigene expression signature was built using 30 training samples, tested on 313 test samples and subsequently validated in a blind study on an independent set of 236 additional tumours.
FINDINGS
The signature accurately classifies patients with respect to overall and progression-free survival (p<0·0001). The signature has a performance, sensitivity, and specificity of 85·4% (95%CI: 77·7–93·2), 84·4% (95%CI: 66·5–94·1), and 86·5% (95%CI: 81·1–90·6), respectively to predict patient outcome. Multivariate analysis indicates that the signature is a significant independent predictor after controlling for currently used riskfactors. Patients with high molecular risk have a higher risk to die from disease and for relapse/progression than patients with low molecular risk (odds ratio of 19·32 (95%CI: 6·50–57·43) and 3·96 (95%CI: 1·97–7·97) for OS and PFS, respectively). Patients with increased risk for adverse outcome can also be identified within the current treatment groups demonstrating the potential of this signature for improved clinical management. These results were confirmed in the validation study in which the signature was also independently statistically significant in a model adjusted for MYCN status, age, INSS stage, ploidy, INPC grade of differentiation, and MKI. The high patient/gene ratio (579/59) underlies the observed statistical power and robustness.
INTERPRETATION
A 59-gene expression signature predicts outcome of neuroblastoma patients with high accuracy. The signature is an independent risk predictor, identifying patients with increased risk in the current clinical risk groups. The applied method and signature is suitable for routine lab testing and ready for evaluation in prospective studies.
FUNDING
The Belgian Foundation Against Cancer, found of public interest (project SCIE2006-25), the Children Cancer Fund Ghent, the Belgian Society of Paediatric Haematology and Oncology, the Belgian Kid’s Fund and the Fondation Nuovo-Soldati (JV), the Fund for Scientific Research Flanders (KDP, JH), the Fund for Scientific Research Flanders (grant number: G•0198•08), the Institute for the Promotion of Innovation by Science and Technology in Flanders, Strategisch basisonderzoek (IWT-SBO 60848), the Fondation Fournier Majoie pour l’Innovation, the Instituto Carlos III,RD 06/0020/0102 Spain, the Italian Neuroblastoma Foundation, the European Community under the FP6 (project: STREP: EET-pipeline, number: 037260), and the Belgian program of Interuniversity Poles of Attraction, initiated by the Belgian State, Prime Minister's Office, Science Policy Programming.
doi:10.1016/S1470-2045(09)70154-8
PMCID: PMC3045079  PMID: 19515614
15.  Clinicopathological Characteristics of Ganglioneuroma and Ganglioneuroblastoma: A Report from the CCG and COG 
Pediatric blood & cancer  2009;53(4):563-569.
Background
The International Neuroblastoma Pathology Classification (INPC) was the first to clearly define prognostic subgroups in ganglioneuroma (GN) and ganglioneuroblastoma (GNB).
Procedure
Histopathology and tumor resectability of 552 GN/GNB cases from the CCG (Children’s Cancer Group) and COG (Children’s Oncology Group) neuroblastoma studies were reviewed. The results were analyzed along with clinical information and biological data of the cases.
Results
According to the INPC, 300 tumors were classified into the Favorable Histology (FH) group and 252 were into the Unfavorable Histology (UH) group. Tumors in the FH group included 43 ganglioneuroma-maturing (GN-M), 198 ganglioneuroblastoma-intermixed (GNB-I), and 59 ganglioneuroblastoma-nodular, favorable subset (GNB-N-FS), and were often (91%) resected completely by single or multiple surgical procedures. Patients with the FH tumors had an excellent prognosis with no tumor-related deaths. The UH group included ganglioneuroblastoma-nodular, unfavorable subset (GNB-N-US) tumors. Patients with the UH tumors had a high incidence (53%) of distant metastasis at the time of diagnosis, and their prognosis significantly depended on clinical stage (5-year EFS: 80.1% for non-stage 4 patients; 16.7% for stage 4 patients): Complete primary tumor resection was not beneficial to those GNB-N-US patients, regardless of whether metastasis was present or not. MYCN amplification was detected in 4 tumors in the FH group and 6 tumors in the UH group. The majority (160/191, 84%) of GN-M and GNB-I tumors had a diploid pattern determined by flow cytometry.
Conclusions
Stringent application of the INPC along with clinical staging was critical for prognostic evaluation of the patients with this group of tumors.
doi:10.1002/pbc.22106
PMCID: PMC2730988  PMID: 19530234
Ganglioneuroma; Ganglioneuroblastoma; International Neuroblastoma Pathology Classification; Clinical Staging; Tumor Resectability; Prognosis

Results 1-15 (15)