Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although pediatric solid tumors are cytogenetically less well characterized than childhood leukemias, an understanding of the role of chromosomal changes in the development of these neoplasms is emerging. The major clinical importance of chromosome analysis today is diagnostic. Especially in small cell round cell tumors of childhood, the unique karyotypic patterns that characterize some of the differential diagnostic entities make it possible to determine with a high degree of certainty which type of cancer the child has. Molecular studies have revealed that almost all retinoblastomas show homozygous loss of function of the RB1 gene in 13q14. At the cytogenetic level, however, aberrations of 13q are seen in less than 25% of retinoblastomas; instead, the presumably progression-related i(6p) and aberrations leading to gain of 1q predominate, each being present in one-third of the tumors. Twenty percent of cytogenetically aberrant Wilms' tumors show structural rearrangements, often deletions, of 11p13 and 11p15, where the WT1 and WT2 genes map. Other frequent changes are trisomy 12 and duplication of 1q. The most common (80%) cytogenetic abnormality in neuroblastoma is loss of distal 1p, a chromosome segment thought to harbor at least two tumor-suppressor genes of importance in tumorigenesis. Double minute chromosomes or homogeneously staining regions are present in one-third of all neuroblastomas and are associated with MYCN amplification. Loss of 1p material or MYCN amplification predicts a poor outcome. The most common (30%) chromosomal aberration in primitive neuroectodermal tumors of the central nervous system is i(17q). The formation of this isochromosome may help inactivate a tumor-suppressor gene located distal to the TP53 locus on 17p. No specific chromosome abnormality has been detected in gliomas, but monosomy 22 and rearrangements leading to loss of 1p and gain of 1q are recurrent. Few hepatoblastomas with chromosomal changes have been reported, but several potential primary aberrations have been described, including +2, +20, and duplication 8q. In Ewing's sarcoma, t(11;22)(q24;q12) is the primary aberration, with trisomy 8 and gain of 1q being frequent secondary changes. Fibrosarcomas in children often carry only numeric aberrations, especially trisomy for chromosomes 11, 20, 17, and 8. Most osteosarcomas are cytogenetically complex, and no specific abnormality has been detected; the single most common change is loss of chromosome 13, which is observed in half the tumors. In contrast, the low-malignancy parosteal osteosarcomas often display supernumerary ring chromosomes as the sole karyotypic deviation. The cytogenetic profiles of rhabdomyosarcomas differ among the various morphologic subtypes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cytogenetic analysis in the examination of solid tumors in children. 794 9

The authors described three cases of intraabdominal desmoplastic small round cell tumour of the peritoneum (IDSRT). In one case the patient was a woman, and in the other two men. The age ranged from 20-29 years. Common of all the cases was a rapid onset of clinical symptoms during the period of twelve to eighteen months. In one case, a 22-year-old woman presented with a symptomless course of disease documented by medical examination one month ago. Intensive chemotherapy was applied but two patients died of generalisation. The 22-year-old woman is alive but with clinical evidence of generalisation in the abdominal cavity. The "classical" type of IDSRT was found in all the cases. Sharply demarcated groups of tumour cells of different size were surrounded by dense fibrous stroma. In some regions desmoplastic areas prevailed. In one case the tumour consisted of round and oval cells resembling a lymphoma. In the other two cases, the slightly elongated cells were present. Immunohistologically, the small round cells were positive for cytokeratins with antibody AE1-AE3. Membrane and dot-like paranuclear positivity were found. In 2 cases the reaction to desmin was seen in a dot-like paranuclear distribution, whereas the reaction to smooth muscle actin (MSA) was negative. In all the cases positivity to vimentin and neuron specific enolase (NSE) were apparent. Negative reactions were found for WT-1 antibody in all three cases. In one of the cases the RT PCR reaction for chimeric gene EWS/WT1 was performed, and found to be negative. Many different tumour types, such as lymphoma, Ewing sarcoma/PNET, neuroblastoma, alveolar rhabdomyosarcoma, malignant mesothelioma must be excluded. Cytogenetic examination should be performed on tumours with a "non-typical" histological pattern and uncommon immunohistological examinations.
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PMID:[Intra-abdominal desmoplastic small-cell tumor of the peritoneum]. 1287 4

Consorcial projects focused on 5 cancer types, breast-, colorectal-, head and neck- and pediatric cancers, and malignant melanoma. Breast cancer studies revealed unique splicing mechanisms concerning BRCA1. In sporadic breast cancers the involvement of DNA-repair genes was proved to be dependent on the histological type. Bone-metastatic tumors have been characterized by decreased NM23 and increased c-met and p53 expressions. C-erbB2 genotype of the primary tumor was not maintained frequently in bone metastases. Application of DNA-microarray and quantitative PCR technologies improved the prediction of therapeutic sensitivity of breast cancers. Colorectal cancer studies revealed regional inhomogenities (clusters) in various geographical regions of Hungary, which were distinct in the case of colonic and rectal cancers. To increase the sensitivity of fecal blood test of colorectal cancer screening, a new double-antibody test was developed and tested in a large cohort of patients. Genetic analysis revealed that hypermethylation is a significant factor in microsatellite instability which, and plays a role in silencing of APC and E-cadherin genes as well. The Hungarian pattern of TS polymorphism was also determined and was correlated not only with the efficacy of 5-FU treatment but with the progression of the disease as well. Population-based studies have been carried out in head and neck cancer patients (HNC) and smokers as well to reveal the genetic background of increasing tumor incidence. These studies revealed polymorphism in XRCC1/3 methylation enzyme gene which has preventive role. Other studies found frequent local immunosuppression in HNC patients. Studies indicated that the success of irradiation in this cancer type is dependent on the anti-vascular effects. Pediatric cancer studies determined the parameters of neuroblastoma screening based on VMA measurements. New splice variants of the WT1 gene involved in the monitoring of MRD of ALL patients was also described this year. We also obtained positive experimental data for the retinoic acid therapy of ALL. Melanoma studies extensively used DNA-microarray technology which identified 4 melanoma-specific and 2 melanoma progression-specific genes. In experimental human melanoma xenograft models we have identified 3 anti-metastatic agents: low molecular weight heparin, 2-methoxyestradiol and erythropoietin-alpha, where the later was characterized by specific effects on tumor vasculature.
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PMID:[Report of the National Oncology Research and Developement Consortium, 2003]. 1510

A new WHO classification of renal cell carcinoma has been introduced in 2004. This classification includes the recently described renal cell carcinomas with the ASPL-TFE3 gene fusion and carcinomas with a PRCC-TFE3 gene fusion. Collectively, these tumors have been termed Xp11.2 or TFE3 translocation carcinomas, which primarily occur in children and young adults. To further study the characteristics of renal cell carcinoma in young patients and to determine their genetic background, 41 renal cell carcinomas of patients younger than 22 years were morphologically and genetically characterized. Loss of heterozygosity analysis of the von Hippel-Lindau gene region and screening for VHL gene mutations by direct sequencing were performed in 20 tumors. TFE3 protein overexpression, which correlates with the presence of a TFE3 gene fusion, was assessed by immunohistochemistry. Applying the new WHO classification for renal cell carcinoma, there were 6 clear cell (15%), 9 papillary (22%), 2 chromophobe, and 2 collecting duct carcinomas. Eight carcinomas showed translocation carcinoma morphology (20%). One carcinoma occurred 4 years after a neuroblastoma. Thirteen tumors could not be assigned to types specified by the new WHO classification: 10 were grouped as unclassified (24%), including a unique renal cell carcinoma with prominently vacuolated cytoplasm and WT1 expression. Three carcinomas occurred in combination with nephroblastoma. Molecular analysis revealed deletions at 3p25-26 in one translocation carcinoma, one chromophobe renal cell carcinoma, and one papillary renal cell carcinoma. There were no VHL mutations. Nuclear TFE3 overexpression was detected in 6 renal cell carcinomas, all of which showed areas with voluminous cytoplasm and foci of papillary architecture, consistent with a translocation carcinoma phenotype. The large proportion of TFE3 "translocation" carcinomas and "unclassified" carcinomas in the first two decades of life demonstrates that renal cell carcinomas in young patients contain genetically and phenotypically distinct tumors with further potential for novel renal cell carcinoma subtypes. The far lower frequency of clear cell carcinomas and VHL alterations compared with adults suggests that renal cell carcinomas in young patients have a unique genetic background.
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PMID:Morphologic and molecular characterization of renal cell carcinoma in children and young adults. 1531 11

Ovarian small cell carcinoma of hypercalcemic type (OSCCHT) is a rare neoplasm with an aggressive behavior, broad differential diagnosis, and unknown histogenesis. To add to knowledge concerning the possible aid of immunohistochemistry in resolving problems in differential diagnosis and to further explore whether that modality points to any specific histogenesis, we undertook an immunohistochemical study of this neoplasm. Fifteen OSCCHTs (including four of the ''large cell" variant) were stained with a range of antibodies, some of which have not been investigated previously in this neoplasm. Cases were stained with AE1/3, EMA, BerEP4, CK5/6, calretinin, WT1, chromogranin, CD56, synaptophysin, CD99, NB84, desmin, S100, CD10, alpha inhibin, TTFI, and p53. Staining was classified as 0 (negative), 1+ (<5% cells positive), 2+ (5% to 25% cells positive), 3+ (26% to 50% cells positive), or 4+ (>50% cells positive). All cases were positive with p53 (two 1+, five 3+, eight 4+), 14 of 15 cases were positive with WT1 (one 1+, thirteen 4+), 14 of 15 with CD10 (three 1+, four 2+, two 3+, five 4+), 13 of 15 with EMA (three 1+, three 2+, two 3+, five 4+), 11 of 15 with calretinin (nine 1+, one 3+, one 4+), 9 of 15 with AE1/3 (eight 1+, one 2+), 4 of 15 with CD56 (one 1+, two 2+, one 4+), 3 of 15 with BerEP4 (two 2+, one 4+), 2 of 15 with synaptophysin (two 1+), and 1 of 15 with S100 (4+). All cases were negative with CK5/6, chromogranin, CD99, NB84, desmin, alpha inhibin, and TTF1. The only noticeable difference in the immunophenotype between typical OSCCHT and the large cell variant was that there was 4 +EMA positivity in three of four cases of large cell variant compared with two of 11 cases of typical OSCCHT. OSCCHT is characteristically positive with AE1/3, EMA, CD10, calretinin, WT1, and p53. Combined EMA and WT1 positivity, the latter usually intense and diffuse, may be of diagnostic value, inasmuch as only a few of the neoplasms in the differential diagnosis are positive with both antibodies. Negative staining with CD99, desmin, NB84, alpha-inhibin, and TTF1 may aid in the cases in which primitive neuroectodermal tumor, rhabdomyosarcoma, intraabdominal desmoplastic small round cell tumor, neuroblastoma, a sex cord-stromal tumor, and metastatic pulmonary small cell carcinoma are in the differential. Calretinin positivity precludes its use in the differential with granulosa cell tumors. The results of this investigation do not settle the issue of histogenesis, which remains enigmatic. The typical age distribution, follicle formation, and calretinin positivity are consistent with a sex cord origin. On the other hand, WT1 and EMA positivity and negative staining with alpha-inhibin would be unusual in a sex cord-stromal neoplasm and can be used as an argument for a surface epithelial origin. Germ cell and neuroendocrine origins seem highly unlikely.
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PMID:An immunohistochemical analysis of ovarian small cell carcinoma of hypercalcemic type. 1538 2

The diagnosis of pediatric tumors relies heavily on immunohistochemical staining of small tissue biopsies, since many entities share a "small blue cell" phenotype. More recently, molecular genetic analysis for detection of specific gene fusion products has become available. With the increased use of such molecular techniques, the authors have noted that tumors with proven molecular diagnoses can exhibit unusual patterns of immunohistochemical staining. This study examines pediatric tumors with a "small blue cell" phenotype in which molecular diagnoses were available where applicable. A panel of immunohistochemical stains was performed (S100, CD56, NB84, CD99 [MIC2], Bcl-2, CD117, CD34, desmin, MNF116, and WT1). In the 370 sections from 37 cases, all primitive neuroectodermal tumors, with and without the presence of t(11;22), demonstrated uniform membranous membrane staining with CD99 (MIC2) and focal staining with CD56, NB84, MNF116, and WT1. All rhabdomyosarcomas, both alveolar and embryonal, demonstrated uniform desmin, CD56, and cytoplasmic WT1 immunostaining. Desmoplastic small round cell tumors showed positive cytokeratin staining, with half having "dot-like" cytoplasmic desmin and WT1 positivity; some showed focal positivity for NB84, CD99, and Bcl-2. The "undifferentiated" sarcomas showed the widest range of staining, with no marker staining all cases. Neuroblastomas exhibited uniform strong staining for CD56 and NB84 and marked cytoplasmic Bcl-2 positivity, and some cases showed cytoplasmic WT1 expression. Blastematous Wilms' tumors showed uniform strong membranous staining for CD56, uniform cytoplasmic staining for Bcl-2, and nuclear expression of WT1. Embryonal pediatric malignancies can demonstrate apparently nonspecific expression patterns for several antigens, which may reflect developmental immaturity rather than specific differentiation pathways.
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PMID:Immunohistochemical findings in embryonal small round cell tumors with molecular diagnostic confirmation. 1572 86

Renal cell carcinomas in young patients constitute a morphologically and genetically heterogeneous group. Twenty percent belong to the newly recognized Xp11.2 translocation-associated family and rare tumors arise from nephroblastoma. Aberrant Wnt signaling through beta-catenin mutation has been implicated in nephroblastoma pathogenesis and has been found to synergize with WT1 mutations. To characterize Wnt signaling activity in renal cell carcinomas in young patients, we gathered 34 tumors (three clear cell, ten Xp11.2 translocation associated, five papillary, two chromophobe, two collecting duct, one neuroblastoma associated, eight unclassified renal cell carcinomas, and three carcinomas combined with nephroblastoma) from patients less than 22 years. Expression of beta-catenin, its homologue gamma-catenin, and of WT1 was assessed by immunohistochemistry in 30 tumors, and sequence analysis of CTNNB1, CTNNG1, and WT1 genes was performed in 25 tumors. Cytoplasmic beta-catenin accumulation was demonstrated in two papillary carcinomas, one neuroblastoma-associated carcinoma, and two carcinomas arising from nephroblastoma. The pattern of gamma-catenin expression paralleled that of beta-catenin but its signal intensity was lower in 22, equal in 7, and stronger only in 1 tumor, respectively. Four tumors showed nuclear WT1 expression. One Xp11.2 translocation-associated carcinoma presented a rare intronic CTNNB1 single nucleotide polymorphism and cytoplasmic beta-catenin accumulation. There were no further CTNNB1 or CTNNG1 sequence alterations. A WT1 mutation was found in the nephroblastoma component of a carcinoma arising from nephroblastoma. These findings suggest Wnt signaling pathway activation only in a minority of renal cell carcinomas in young patients. CTNNB1 mutations are rare events. Cytoplasmic beta-catenin accumulation in an Xp11.2-associated carcinoma suggests potential interaction of Wnt signaling components with microphthalmia transcription factor family also in Xp11.2 translocation carcinomas. WT1 mutation in the nephroblastoma component of a mixed-type renal cell carcinoma provides direct evidence for clonal independence of nephroblastoma and carcinoma components in this exceptional tumor.
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PMID:Wnt signaling pathway analysis in renal cell carcinoma in young patients. 1787 95

Hepatoblastoma is a malignant tumor that typically presents as a mass in the liver of a child less than 5 years of age. The diagnosis is usually established by means of a needle core biopsy before the treatment is commenced. The pathologic diagnosis of hepatoblastoma relies on the microscopic identification of typical morphologic features, but these may not be present in a needle core biopsy, and in this setting immunohistochemical staining has an important role in the exclusion of other childhood malignancies. We have studied 12 needle core biopsies from cases of hepatoblastoma, all of which had the diagnosis confirmed by subsequent resection of the tumor, to determine if these tumors show a diagnostic phenotype. The needle biopsies were immunostained with a standard panel of antibodies normally used in the characterization of childhood small round blue cell tumors, with the addition of antibodies directed against alpha-fetoprotein and alpha-1-antitrypsin. Our results indicate that the majority of hepatoblastomas expressed cytokeratins (10/12) and that alpha-1-antitrypsin and alpha-fetoprotein staining were positive in approximately half the cases (5/12 and 7/12, respectively). We also observed frequent expression of antigens normally expressed on other childhood tumors. A significant number of hepatoblastomas (8/12) expressed MIC-2 (CD99) an antigen normally associated with primitive neuroectodermal tumor, 4 cases showed positive staining with the neural-associated antigen NCAM (CD56), and 3 were positive with the neuroblastoma marker NB84. Occasional cases showed expression of the muscle marker desmin (2/12) and 2 cases stained with BCL2. Vimentin expression was seen in 1 case, and a single case also expressed the neural markers PGP9.5 and neurone-specific enolase. In all cases, the tumor cells were negative with CD45, WT1, and S-100. These findings indicate that the primitive cells in hepatoblastoma have a variable immunophenotype and can express antigens normally seen in other childhood malignancies. In the clinical setting of the differential diagnosis of childhood abdominal mass, hepatoblastoma shows no distinct immunohistochemical profile, and the diagnosis requires a combination of the clinical, imaging, and pathologic findings.
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PMID:Variable antigen expression in hepatoblastomas. 1822 29

Fine needle aspiration cytology (FNAC) is used for preoperative diagnosis of paediatric renal tumours, especially in centres where preoperative chemotherapy is advocated in Wilms' tumour. This review focuses on salient cytological features in specific paediatric renal tumours, the approach to resolving a differential diagnosis and the role of ancillary methods in diagnosis of paediatric renal tumours. Crucial differential diagnoses include distinguishing: Wilms' tumour from benign tumours in the kidney like multicystic nephroma or congenital mesoblastic nephroma; aggressive non-Wilms' tumours of kidney like rhabdoid tumour of kidney; and Wilms' tumour from other paediatric round cell sarcomas like neuroblastoma, non-Hodgkin lymphoma etc. An approach based on classifying smears according to their cellular patterns as triphasic, round cell, spindle cell or epithelioid cell type assists in classifying paediatric renal tumours on cytology. Immunocytochemistry for WT1, cytokeratin, synaptophysin, leucocyte common antigen and MIC2 will aid in evaluating round cell tumours in the renal region, while WT1, bcl2, vimentin and desmin will be useful for spindle cell tumours in that region. Extra material can also be evaluated for demonstration of specific cytogenetic abnormalities in these tumours. A checklist of common tumours in a particular age group, relevant clinical information, awareness of distinctive and overlapping cytological features, and appropriate use of immunocytochemistry with cytogenetics go a long way in ensuring an accurate cytological diagnosis. Used judiciously, FNAC is as effective a tool as a core biopsy for preoperative diagnosis of paediatric renal tumours, and with experience a 92% accuracy rate can be achieved.
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PMID:The cytological diagnosis of paediatric renal tumours. 1970 Apr 11

We evaluated the feasibility and usefulness of reverse transcriptase-polymerase chain reaction (RT-PCR) on fine-needle aspirates for categorization of small blue round cell tumors (SBRCTs). A total of 51 cases, including 25 Ewing sarcoma/peripheral primitive neuroectodermal tumors (PNETs), 11 rhabdomyosarcomas, 13 neuroblastomas, and 2 desmoplastic small round cell tumors (DSRCTs) were analyzed. The detection of the EWS-FLI1 (20/25) and EWS-ERG (4/25) fusion transcripts resolved 24 of 25 cases of Ewing sarcoma/PNET. The PAX3/7-FKHR fusion transcript was detected in 2 of 4 cases of alveolar rhabdomyosarcoma and the EWS-WT1 transcript in both cases of DSRCT. Tyrosine hydroxylase and 3,4-dihydroxyphenylalanine (dopa) decarboxylase transcripts were demonstrated in 10 of 13 cases of neuroblastoma. In comparison, immunocytochemical analysis resolved 19 (76%) of 25 Ewing sarcomas, 9 (82%) of 11 rhabdomyosarcomas, 6 (46%) of 13 neuroblastomas, and 1 (50%) of 2 DSRCTs. Overall, RT-PCR resolved 38 (86%) of 44 vs 35 (69%) of 51 cases by immunocytochemical analysis. RT-PCR is easily applied to fine-needle aspirates of SBRCT and greatly facilitates accurate tumor typing.
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PMID:Reverse transcriptase-polymerase chain reaction as an ancillary molecular technique in the diagnosis of small blue round cell tumors by fine-needle aspiration cytology. 2023 17


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