Pediatric Neoplasia Research Articles

Pediatric Neuroendocrine Neoplasia of the Parathyroid Glands: Delving into Primary Hyperparathyroidism.

Our objective was to overview the most recent data on primary hyperparathyroidism (PHP) in children and teenagers from a multidisciplinary perspective. Methods: narrative review based on full-length, English-language papers (from PubMed, between January 2020 and July 2023). Results: 48 papers (14 studies of ≥10 subjects/study, and 34 case reports/series of <10 patients/study). Study-sample-based analysis: except for one case-control study, all of the studies were retrospective, representing both multicenter (n = 5) and single-center (n = 7) studies, and cohort sizes varied from small (N = 10 to 19), to medium-sized (N = 23 to 36) and large (N = 63 to 83); in total, the reviewed studies covered 493 individuals with PHP. Case reports/series (n = 34, N = 41): the mean ages studied varied from 10.2 to 14 years in case reports, and the mean age was 17 years in case series. No clear female predominance was identified, unlike that observed in the adult population. Concerning the assessments, there were four major types of endpoints: imaging data collection, such as ultrasound, 99mTc Sestamibi, or dual-phase computed tomography (CT); gene testing/familial syndrome identification; preoperative findings; and exposure to surgical outcome/preoperative drugs, like cinacalcet, over a 2.2-year median (plus two case reports of denosumab used as an off-label calcium-lowering agent). Single-gland cases (representing 85% of sporadic cases and 19% of genetic PHP cases) showed 100% sensitivity for neck ultrasounds, with 98% concordance with 99mTc Sestamibi, as well as a 91% sensitivity for dual-phase CT, with 25% of the lesions being ectopic parathyroids (mostly mediastinal intra-thymic). Case reports included another 9/41 patients with ectopic parathyroid adenomas, 3/41 with parathyroid carcinomas, and 8/41 subjects with brown tumors. Genetic PHP (which has a prevalence of 5-26.9%) mostly involved MEN1, followed by CDC73, CASR, RET, and CDKN1B, as well as one case of VHL. Symptomatic PHP: 70-100% of all cases. Asymptomatic PHP: 60% of genetic PHP cases. Renal involvement: 10.5% of a cohort with genetic PHP, 71% of sporadic PHP cases; 50% (in a cohort with a mean age of 16.7), 29% (in a cohort with a mean age of 15.2); 0% (in infancy) to 50-62% (in teenagers). Bone anomalies: 83% of the children in one study and 62% of those in two other studies. Gastrointestinal issues: 40% of one cohort, but the data are heterogeneous. Cure rate through parathyroidectomy: 97-98%. Recurrent PHP: 2% of sporadic PHP cases and 38% of familial PHP cases. Hungry bone syndrome: maximum rate of 34-40%. Case reports identified another 7/41 subjects with the same post-parathyroidectomy condition; a potential connection with ectopic presentation or brown tumors is suggested, but there are limited data. Minimally invasive thoracoscopic approaches for ectopic tumors seemed safe. The current level of statistical evidence on pediatric PHP qualifies our study- and case-sample-based analysis (n = 48, N = 534) as one of the largest of its kind. Awareness of PHP is the key factor to benefit our young patients.

DICER1 Mutations Do Not Always Indicate Dismal Prognosis in Pediatric Poorly Differentiated Thyroid Carcinomas.

Progress in the field of pediatric thyroid pathology has linked DICER1 mutations to benign follicular cell-derived thyroid tumors (e.g., follicular adenoma with papillary architecture, follicular nodular disease), low-risk follicular cell-derived differentiated thyroid carcinomas and PDTCs enriched in fatal or recurrent/progressive disease. The dismal outcome of DICER1-harboring pediatric PDTCs stems from a limited number of reported patients' data given the rarity of pediatric PDTCs. In light of the former observations, the current study assessed clinicopathological variables of a series of 5 pediatric (≤ 18 years old) PDTCs using the Turin criteria (WHO 2022) and also examined the status of DICER1 and TERT promoter mutations. Five PDTCs (3 males, 2 females) were included in the study. The mean age at the time of diagnosis was 15.4 years. No patients had a history of DICER1 syndrome-related tumors or other clinicopathological diagnostic features of DICER1 syndrome. The mean tumor size was 3.9 cm. All tumors were completely submitted for microscopic examination. There was increased mitotic activity ranging from 3 to 10 mitoses per 2 mm2. Tumor necrosis was present in two cases. No PDTC harbored TERT promoter mutation. DICER1 hot spot mutation was identified in one (20%) tumor. The DICER1-mutant tumor had neither associated differentiated thyroid carcinoma component nor other pathological findings in the adjacent thyroid parenchyma. The DICER1-mutant PDTC showed widely invasive growth confined to the thyroid parenchyma. Despite the widely invasive growth, the tumor lacked vascular invasion. Two DICER1 wild-type PDTCs had lymphocytic thyroiditis and another one had underlying follicular nodular disease and/or follicular adenomas. Three DICER1 wild-type PDTCs also had an associated differentiated thyroid carcinoma component with no high-grade features. No abnormal p53 expression (overexpression or global loss) was recorded in all tested tumors. Four patients had follow-up data with a mean follow-up time of 60.25 months (range: 18-86 months). One patient with no evidence of disease recurrence died of anunrelated cause after 18 months of the initial surgery, all remaining patients were alive with no distant metastasis at their last visit. Of the 4 patients with lymph node (LN) dissection, one DICER1 wild-type PDTC had recurrent nodal disease. During the follow-up period (72 months), no local recurrence or distant metastases was detected in the DICER1-mutant PDTC. Taken together all reported findings from earlier series, DICER1 mutations alone may not necessarily indicate dismal outcome in a subset of pediatric PDTCs. The occurrence of additional genomic alterations as discussed in some earlier reports may be contributing to tumor progression or aggressivity of pediatric PDTCs. The lack of vascular invasion in the current DICER1-mutant pediatric PDTC may also explain an indolent biologic outcome. The risk escalation of DICER1 mutations should integrate the status of additional genetic events and well-established pathologic variables in order to ensure predictive dynamic risk stratification in DICER1-mutant pediatric PDTCs. Additional studiesare needed to corroborate the findings of this study and advance our knowledge in pediatric thyroid neoplasia.

TREATMENT/MANAGEMENT OF OTHER HEPATIC TUMORS

Pediatric liver neoplasias are rare, comprising 1–4% of all solid childhood tumors. More than half of these masses are due to hepatoblastoma and hepatocellular carcinomas, making remaining various liver tumors much more rarer. Hepatic mesenchymal hamartoma (HMH) is a benign tumor observed in children less than five- year-old. It is located in the right lobe of the liver more often. It has a cystic structure, and AFP is generally normal or slightly elevated. The treatment is complete resection. In rare cases, HMH can transform into undifferentiated embryonal sarcoma. Focal nodular hyperplasia is a well-circumscribed benign lesion, which is usually discovered incidentally as well as with oral contraceptive use, postchemotherapy status, and hereditary hemorrhagic telengiectasia. Typical imaging finding is a central scar in the mass lesion, which might overlap with fibrolamellar hepatocellular carcinoma. Asymptomatic cases might be managed with an expectant approach by careful monitoring whereas symptomatic cases might be treated with surgery or ablation therapy. Infantile hemangioma is the most common benign hepatic tumor in infancy. Symptoms at admission may include abdominal distention due to hepatomegaly, congestive heart failure, feeding problems, anemia, thrombocytopenia and consumptive coagulopathy, jaundice. Many of these hemangiomas are discovered incidentally and are localized. In most cases, these lesions are small enough to be of no clinical significance. In severe cases, propranolol, corticosteroids, mTOR inhibitors or cytotoxic agents can be used for treatment. Undifferentiated embryonal sarcoma of the liver (UESL) is the third most common malignant liver tumor in children. The median age of diagnosis of UESL is 10,5 years, in comparison to that of liver rhabdomyosarcoma which is 3.6 years. UESL is an aggressive malignancy that should be treated with multimodal therapy. Most important prognostic factor is the completeness of the resection. The survival is reported to range between 70% and 90% in various case series. Rhabdomyosarcomas are observed in the biliary tract. The usual sign in admission is obstructive jaundice with or without abdominal mass. Treatment is multimodal therapy. With CWS protocols, the 5-year overall (OS) and event free survival (EFS) rates were 58% and 47%, respectively. Hepatic angiosarcoma is a rare but highly aggressive malignancy of endothelial cells, previously known as infantile hemangioendothelioma type 2. There is a girl predominance. Despite multiagent aggressive treatment approaches including liver transplantation, the overall prognosis is still poor.

Predictive Value of miRNA-181a in Pediatric Acute Lymphoblastic Leukemia

Background: Acute lymphoblastic leukemia (ALL), a common pediatric malignant neoplasia, showed high relapse rate after induction therapy. Some miRNAs have been shown to regulate normal hematopoiesis and their disruption could contribute to leukemogenesis: Recently, specific miRNA, including miR-181a, was shown to be involved in the pathogenesis of ALL, serving as a biomarker for diagnosis and relapse of ALL. Aim of the Study: To evaluate miR-181a expression level as a predictive marker for children with acute lymphoblastic leukemia. Patients and Methods: 40 pediatric ALL patients were included in this study. miR-181a expression was assessed at diagnosis before start of treatment. Samples were either peripheral blood or bone marrow aspirate sample. Patients were evaluated clinically and laboratory after the induction therapy. Results: The remission rate was significantly higher in patients with high miR-181a expression compared to those with low expression (p Conclusion: The expression level of miR-181a was significantly higher in remission group than in non-remission group was and predict good response to induction therapy.

Biology and targeting of the Jumonji-domain histone demethylase family in childhood neoplasia: a preclinical overview

ABSTRACTIntroduction: Epigenetic mechanisms of gene regulatory control play fundamental roles in developmental morphogenesis, and, as more recently appreciated, are heavily implicated in the onset and progression of neoplastic disease, including cancer. Many epigenetic mechanisms are therapeutically targetable, providing additional incentive for understanding of their contribution to cancer and other types of neoplasia.Areas covered: The Jumonji-domain histone demethylase (JHDM) family exemplifies many of the above traits. This review summarizes the current state of knowledge of the functions and pharmacologic targeting of JHDMs in cancer and other neoplastic processes, with an emphasis on diseases affecting the pediatric population.Expert opinion: To date, the JHDM family has largely been studied in the context of normal development and adult cancers. In contrast, comparatively few studies have addressed JHDM biology in cancer and other neoplastic diseases of childhood, especially solid (non-hematopoietic) neoplasms. Encouragingly, the few available examples support important roles for JHDMs in pediatric neoplasia, as well as potential roles for JHDM pharmacologic inhibition in disease management. Further investigations of JHDMs in cancer and other types of neoplasia of childhood can be expected to both enlighten disease biology and inform new approaches to improve disease outcomes.

Therapeutic potential of nvp-bkm120 in human osteosarcomas cells.

Osteosarcoma (OS) is the most common pediatric malignant neoplasia of the skeletal system. It is characterized by a high degree of malignancy and a severe tendency to metastasize. In the past decade, many studies have provided evidence that the phosphoinositide 3-kinase (PI3K) signaling pathway is one of the most frequently altered pathways in human cancer, and has a critical role in driving tumor initiation and progression. Here, we have analyzed the therapeutic potential of the pan-PI3K inhibitor NVP-BKM120, which has recently entered clinical Phase II for treatment of PI3K-dependent cancers on three OS cell lines. We observed a concentration- and time-dependent decrease of Ser473 p-Akt as well as reduced levels of Thr37/46 p-4E-BP1, an indicator of the mammalian target of rapamycin complex 1 activity. All OS cell lines used in this study responded to BKM120 treatment with an arrest of cell proliferation, an increase in cell mortality, and an increase in caspase-3 activity. MG-63 cells were the most responsive cell line, demonstrating a significant increase in sub-G1 cells, and a rapid induction of cell death. Furthermore, we demonstrate that BKM120 is more effective when used in combination with other standard chemotherapeutic drugs. Combining BKM120 with vincristine demonstrated a more synergistic effect than BKM120 with doxorubicin in all the lines. Hence, we suggest that BKM120 may be a novel therapy for the treatment of OS presenting with anomalous upregulation of the PI3K signaling pathway.

Colorectal carcinoma in a 9-year-old boy

While colorectal carcinoma is a common tumor entity in adults, it is extremely rare in children with an incidence of 1:1000000 and represents a minor proportion of pediatric neoplasia cases with an incidence of less than 1%. If colorectal carcinoma occurs, the outcome is often fatal due to aggressive tumor biology with mostly mucinous, poorly differentiated, and aggressively growing tumors; the clinical symptoms are often attributed too late to a malignancy. The present report describes the case of a 9-year-old boy who presented with complaints of general weakness and recurrent abdominal pain, caused by an adenocarcinoma of the ascending colon (T3 N1 M0). After right hemicolectomy, chemotherapy was performed using the FOLFOX 4 scheme. To our knowledge, this case report is of the youngest patient affected by a primary, non-syndrome-associated colorectal adenocarcinoma.

GLUT1 expression in pediatric adrenocortical tumors: a promising candidate to predict clinical behavior

BackgroundDiscrimination between benign and malignant tumors is a challenging process in pediatric adrenocortical tumors. New insights in the metabolic profile of pediatric adrenocortical tumors may contribute to this distinction, predict prognosis, as well as identify new molecular targets for therapy. The aim of this work is to characterize the expression of the metabolism-related proteins MCT1, MCT2, MCT4, CD147, CD44, GLUT1 and CAIX in a series of pediatric adrenocortical tumors.MethodsA total of 50 pediatric patients presenting adrenocortical tumors, including 41 clinically benign and 9 clinically malignant tumors, were included. Protein expression was evaluated using immunohistochemistry in samples arranged in tissue microarrays.ResultsThe immunohistochemical analysis showed a significant increase in plasma membrane expression of GLUT1 in malignant lesions, when compared to benign lesions (p=0.004), being the expression of this protein associated with shorter overall and disease-free survival (p=0.004 and p=0.001, respectively). Although significant differences were not observed for proteins other than GLUT1, MCT1, MCT4 and CD147 were highly expressed in pediatric adrenocortical neoplasias (around 90%).ConclusionGLUT1 expression was differentially expressed in pediatric adrenocortical tumors, with higher expression in clinically malignant tumors, and associated with shorter survival, suggesting a metabolic remodeling towards a hyperglycolytic phenotype in this malignancy.

Two Classic Patterns of Pediatric Renal Neoplasia.

HomeRadioGraphicsVol. 36, No. 2 PreviousNext IlluminationsTwo Classic Patterns of Pediatric Renal NeoplasiaAletta Ann Frazier Aletta Ann Frazier Author AffiliationsAmerican Institute for Radiologic Pathology, Silver Spring, Maryland, and University of Maryland School of Medicine, Baltimore, Maryland ([email protected])Aletta Ann Frazier Published Online:Mar 10 2016https://doi.org/10.1148/rg.2016164002MoreSectionsFull textPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In Article HistoryPublished online: Mar 10 2016Published in print: Mar 2016 FiguresReferencesRelatedDetailsRecommended Articles Renal Tumors of Childhood: Radiologic-Pathologic Correlation Part 1. The 1st Decade: From the Radiologic Pathology ArchivesRadioGraphics2016Volume: 36Issue: 2pp. 499-522Imaging of Kidney Cysts and Cystic Kidney Diseases in Children: An International Working Group Consensus StatementRadiology2019Volume: 290Issue: 3pp. 769-782Hereditary Renal Cystic Disorders: Imaging of the Kidneys and BeyondRadioGraphics2017Volume: 37Issue: 3pp. 924-946Renal Neoplasms in Young AdultsRadioGraphics2022Volume: 42Issue: 2pp. 433-450Renal Tumors of Childhood: Radiologic-Pathologic Correlation Part 2. The 2nd Decade: From the Radiologic Pathology ArchivesRadioGraphics2017Volume: 37Issue: 5pp. 1538-1558See More RSNA Education Exhibits Pediatric Renal Masses and Their Mimics: A Pictorial ReviewDigital Posters2020Beyond Renal Cell Carcinoma – MRI Characteristics of Non-RCC Renal TumorsDigital Posters2020Nonmalignant Renal and Perirenal Masses: Can They Be Differentiated from Malignancy?Digital Posters2018 RSNA Case Collection Wilms tumorRSNA Case Collection2020Xanthogranulomatous PyelonephritisRSNA Case Collection2021Renal LymphomaRSNA Case Collection2021 Vol. 36, No. 2 Metrics Altmetric Score PDF download

Pediatric Spinal Neoplasia: A Practical Imaging Overview of Intramedullary, Intradural, and Osseous Tumors

Imaging of the pediatric spine can be a daunting task for pediatric radiologists, neuroradiologists, and musculoskeletal imagers alike. This is in large part consequent to multiple differential considerations that are frequently specific to this patient population. Though a definitive diagnosis is not always possible through imaging, determining an appropriate anatomical compartment facilitates a more focused differential list, and therefore provides value to the treating providers. This is typically achieved with magnetic resonance imaging and computed tomography. The purpose of this paper is to equip the radiologist with a useful approach to the imaging of, and creating a practical differential for tumors of the pediatric spine. This includes intramedullary, intradural, and osseous pathology. We focus on the most commonly encountered lesions in each of the above compartments. We discuss less common lesions where appropriate owing to their incidence in the adult spine or pediatric extraspinal locations, and are often included in imaging reports or tumor board discussions. As such, this review offers the radiologist a reasonable and reproducible framework for imaging and diagnosing the vast majority of lesions encountered in the pediatric spine.

A “Twist box” Code of p53 Inactivation: Twist box:p53 Interaction Promotes p53 Degradation

Twist proteins have been shown to contribute to cancer development and progression by impinging on different regulatory pathways, but their mechanism of action is poorly defined. By investigating the role of Twist in sarcomas, we found that Twist1 acts as a mechanism alternative to TP53 mutation and MDM2 overexpression to inactivate p53 in mesenchymal tumors. We provide evidence that Twist1 binds p53 C terminus through the Twist box. This interaction hinders key posttranslational modifications of p53 and facilitates itsMDM2-mediated degradation. Our study suggests the existence of a Twist box code of p53 inactivation and provides the proof of principle that targeting the Twist box:p53 interaction might offer additional avenues for cancer treatment.

MicroRNA expression and activity in pediatric acute lymphoblastic leukemia (ALL)

Acute lymphoblastic leukemia (ALL) is the most common type of pediatric neoplasia. Highly heterogeneous, ALL includes several genetic subtypes with varying clinical outcome. Although, some features are well established as prognostic predictors, the details of the molecular mechanisms underlying different phenotypes are only beginning to emerge. Recently, microRNAs (miRNAs) have been shown to influence a range of physiological processes and, consequently, alterations in their expression and functions have been associated with the development of many cancers, including leukemia. This article aims to review the current state of knowledge of the role of miRNAs on the biology of childhood ALL, also including relevant findings from the adult leukemia literature.

AML1/RUNX1 gene point mutations in childhood myeloid malignancies

Currently, it is widely accepted that one of the crucial players in adult leukemic transformation is the RUNX1 gene. However, there is little data available regarding whether mutations in this gene also contribute to pediatric leukemia, especially in childhood myeloid malignancies. Therefore we made a decision to screen patients with pediatric myeloid neoplasias for the presence of RUNX1 mutations in their samples. Patients (n = 238) with diagnoses of de novo acute myeloid leukemia (AML) (n = 198), de novo myelodisplastic syndrome (MDS) (n = 16), therapy-related AML (n = 9), juvenile myelomonocytic leukemia (JMML) (n = 15) were included in this study. All patients were Belarusians between the ages of 0 and 18 years. The frequency of RUNX1 point mutations in the total group of patients with de novo AML was 3% and de novo MDS was 15%. Cooperation of point mutations in the RUNX1 and NRAS genes, and the cytogenetic abnormality, -7/7q-, was demonstrated in children with therapy-related AML. RUNX1 point mutations predominate in those de novo AML and MDS patients with a normal karyotype in leukemic cells. Frequency of RUNX1 point mutations was about 4% in a group of children with de novo AML aged 0-14 years diagnosed during the period of 1998-2009. During the course of this investigation, valuable data were obtained concerning RUNX1 gene mutation frequencies in different clinical, morphological, and cytogenetic groups of patients with myeloid malignancies, and its cooperation with other molecular aberrations.

Oxygen-Dependent Gene Expression in Development and Cancer: Lessons Learned from the Wilms’ Tumor Gene, WT1

Adequate tissue oxygenation is a prerequisite for normal development of the embryo. Most fetal organs are exquisitely susceptible to hypoxia which occurs when the delivery of oxygen is exceeded by the actual demand. Developmental abnormalities due to insufficient supply with oxygen can result from the impaired expression of genes with essential functions during embryogenesis. As such, the Wilms’ tumor gene, WT1, is among the fetal genes that are regulated by the local oxygen tension. WT1 was originally discovered as a tumor suppressor gene owing to loss-of-function mutations in a subset of pediatric renal neoplasias, known as nephroblastomas or Wilms’ tumors. Wilms’ tumors can arise when pluripotent progenitor cells in the embryonic kidney continue to proliferate rather than differentiating to glomeruli and tubules. WT1 encodes a zinc finger protein, of which multiple isoforms exist due to alternative mRNA splicing in addition to translational and post-translational modifications. While some WT1 isoforms function as transcription factors, other WT1 proteins are presumably involved in post-transcriptional mRNA processing. However, the role of WT1 reaches far beyond that of a tumor suppressor as homozygous disruption of Wt1 in mice caused embryonic lethality with a failure of normal development of the kidneys, gonads, heart, and other tissues. WT1 mutations in humans are associated with malformation of the genitourinary system. A common paradigm of WT1 expressing cells is their capacity to switch between a mesenchymal and epithelial state. Thus, WT1 likely acts as a master switch that enables cells to undergo reciprocal epithelial-to-mesenchymal transition. Impairment of renal precursor cells to differentiate along the epithelial lineage due to WT1 mutations may favor malignant tumor growth. This article shall provide a concise review of the function of WT1 in development and disease with special consideration of its regulation by molecular oxygen.

Pediatric brain tumors: a histologic and genetic update on commonly encountered entities

As our understanding of pediatric brain neoplasia flourishes, so does the development of diagnostic, prognostic, and predictive biomarkers. The neuropathologist uniquely stands at the crossroads between pathology and molecular genetics, often overseeing the creation, development, implementation, delivery, and reporting of the newest bioassays. This review serves to highlight the key microscopic and genetic features of the most common pediatric brain tumors. For example, INI-1 immunohistochemistry has assisted in identifying several previously unrecognized cases of rhabdoid cell-poor atypical teratoid rhabdoid tumor (ATRT). The latest discovery involving the tandem duplication and fusion BRAF-KIAA1549 on chromosome 7q34 in pilocytic astrocytoma has drawn attention to the MAPK-ERK pathway and its potential chemotherapeutic manipulation. The newly identified IDH1 mutation, which appears characteristic of "secondary astrocytomas," has yet to be studied in the pediatric population, but some researchers have extolled concomitant BRAF-KIAA1549/IDH1 analysis in the neuropathologic workup of many astrocytomas. Through these and other advances, our understanding of pediatric brain tumors will continue to expand exponentially, and as such will set the stage for truly effectual future treatments.

High Erk-1 activation and Gadd45a expression as prognostic markers in high risk pediatric haemolymphoproliferative diseases

Studies on activated cell-signaling pathways responsible for neoplastic transformation are numerous in solid tumors and in adult leukemias. Despite of positive results in the evolution of pediatric hematopoietic neoplasias, there are some high-risk subtypes at worse prognosis. The aim of this study was to asses the expression and activation status of crucial proteins involved in cell-signaling pathways in order to identify molecular alterations responsible for the proliferation and/or escape from apoptosis of leukemic blasts. The quantitative and qualitative expression and activation of Erk-1, c-Jun, Caspase8, and Gadd45a was analyzed, by immunocytochemical (ICC) and western blotting methods, in bone marrow blasts of 72 patients affected by acute myeloid leukemia (AML), T-cell acute lymphoblastic leukemia (ALL) and stage IV non-Hodgkin Lymphoma (NHL). We found an upregulation of Erk-1, Caspase8, c-Jun, and Gadd45a proteins with a constitutive activation in 95.8%, 91.7%, 86.2%, 83.4% of analyzed specimens, respectively. It is worth noting that all AML patients showed an upregulation of all proteins studied and the high expression of GADD45a was associated to the lowest DFS median (p = 0.04). On univariate analysis, only Erk-1 phosphorylation status was found to be correlated with a significantly shorter 5-years DFS in all disease subgroups (p = 0.033) and the lowest DFS median in ALL/NHL subgroup (p = 0.04). Moreover, the simultaneous activation of multiple kinases, as we found for c-Jun and Erk-1 (r = 0.26; p = 0.025), might synergistically enhance survival and proliferation potential of leukemic cells. These results demonstrate an involvement of these proteins in survival of blast cells and, consequently, on relapse percentages of the different subgroups of patients.

Comparison of different techniques for the detection of genetic risk-identifying chromosomal gains and losses in neuroblastoma

Neuroblastoma (NB) is a pediatric neoplasia that shows complex combinations of acquired genetic aberrations. The specific genes and the molecular mechanisms responsible for development and progression of NB remain poorly understood. Our main objective is to compare the results obtained with different techniques for the detection of genomic data in 20 patients with NB using the information obtained to select the appropriate technique in routine analysis for the therapeutic stratification. The genetic methods used in this study are multiprobe fluorescence in situ hybridization (FISH) assay, metaphasic comparative genomic hybridization (mCGH), array comparative genomic hybridization (aCGH), and the multiplex ligation-dependent probe amplification (MLPA). Genomic copy number abnormalities were used to group the cases in four categories: MYCN amplification cases; 11q deletion tumors; cases with partial chromosome gains or losses and samples with entire chromosome alterations. The data obtained from the multigenomic techniques showed a high degree of concordance and our findings support the hypothesis that NB consists of biologically distinct subgroups that differ by genetic characteristics of prognostic relevance. FISH will be essential for the mandatory study of MYCN status. The use of MLPA as routine technique is an advantage procedure for detecting the implication of the common genetic alterations in NB.

How a rare pediatric neoplasia can give important insights into biological concepts: a perspective on juvenile myelomonocytic leukemia

Representing as little as 2% of hematopoietic malignancies in childhood, juvenile myelomonocytic leukemia (JMML) has nevertheless formed the basis of a fascinating chapter of biomedical research on hematopoietic neoplasia over the past two decades. It not only furthered our understanding of one of

Thyroid cancer in childhood: Management strategy, including dosimetry and long-term results

Thyroid cancer, although very rare in childhood, represents the most common pediatric endocrine neoplasia. The low incidence and the resulting limited availability of prospective, randomized trials lead to a lack of evidence- based recommendations for treatment strategies. Total thyroidectomy and lymphadenectomy, when indicated, followed by ablative radioiodine treatment, are considered the cornerstones of initial patient management which decrease the risk of relapse. On the other hand, less aggressive treatment modalities should also be aimed at due to the high life expectancy of this special patient group and the potential impairment of the quality of life. These considerations have led to individualized "tailored" therapeutic approaches based on prior risk stratification. This article mainly deals with novel nuclear medicine concepts for dosing regimens in radioiodine therapy.

FOXG1 is overexpressed in hepatoblastoma

Bacterial artificial chromosome array comparative genomic hybridization analysis of hepatoblastomas reveals a deletion in the 14q12 locus in 12 of 16 cases. A high frequency of copy gain is seen on chromosomes 1q, 2, 5p, 8, and 20. Frequent deletions are also seen at 6q, 17q, and 1p with less frequent gains on 4p, 6p, and 19p. 14q12 deletion locus analyses using quantitative real-time polymerase chain reaction reveals copy number gain/amplification in the region immediately telomeric to the deleted locus, including copy number gain (2- to 4-fold) of FOXG1 in 13 out of 16 tumors. This is associated with up-regulation (approximately 87-fold) of FOXG1 gene transcripts and increased protein expression. Immunostaining reveals an inverse relationship between FOXG1 expression and p21cip1 expression in all histologic subtypes. However, FOXG1 transcript levels were significantly higher (approximately 75-fold) in tumors with embryonal and small cell components when compared with pure fetal hepatoblastomas. FOXG1 has been implicated in the repression of transforming growth factor beta-induced expression of p21cip1 and cytostasis. Our findings are consistent with such a role for FOXG1. We propose that FOXG1 overexpression may contribute to the maintenance of the undifferentiated state in hepatoblastomas and could be a potential target for molecular therapeutics. This is the first report of a possible role for FOXG1 in hepatoblastoma and pediatric neoplasia.