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PubMed1989

Analysis of nerve growth factor receptor expression in human neuroblastoma and neuroepithelioma cell lines.

A series of 22 neuroepithelioma and neuroblastoma cell lines were screened for expression of nerve growth factor receptor (NGFR) by flow cytometry, Western blotting, and Northern blotting. All 5 neuroepithelioma cell lines expressed cell surface NGFR, with 30-69% of cells NGFR positive, but the 17 neuroblastoma cell lines tested had a smaller percentage of cell surface NGFR-positive cells (0-21%) and 10 lines were completely lacking cell surface NGFR. SY5Y, a variant line with a neuronal phenotype derived from neuroblastoma line SKNSH, expressed much more NGFR than SHEP, a variant line with an epithelial-like phenotype also derived from SKNSH. By Western blotting, the Mr approximately 69,000 NGFR band was detected for all four neuroepithelioma cell lines tested but was visible for only 8 of 15 neuroblastoma cell lines tested. The band was most intense for neuroepithelioma cell lines SKNMC and TC32. For these two lines, a Mr approximately 56,000 and a Mr approximately 60,000 band were also detected. By Northern blotting, all three neuroepithelioma cell lines tested were positive for the 3.8 kilobase NGFR mRNA, but only 8 of 15 neuroblastoma cell lines were positive. Neuroepithelioma cell line TC32 and neuroblastoma cell line GICAN had the strongest expression of NGFR mRNA. These results demonstrate that NGFR is a biological marker for neuroepithelioma and that NGFR expression is heterogeneous for neuroblastoma cell lines. This series of neural cell lines differing in NGFR expression will be useful for future studies of regulation of NGFR expression and neuronal differentiation.

Antibodies, Monoclonal↗

PubMed1989

Expression of the cholecystokinin gene by cultured human primitive neuroepithelioma cell lines.

In this report we identify two cultured human primitive neuroepithelioma cell lines that express cholecystokinin (CCK) RNA and synthesize substantial amounts of pro-CCK, but differ in their ability to process the prohormone. Seven cultured human neural tumor lines, including two primitive neuroepitheliomas and five neuroblastomas, were screened for CCK gene expression using a CCK C-terminal RIA system, a RIA specific for the carboxy-terminal extension of prepro-CCK, and RNAse protection assays specific for CCK mRNA. RNA derived from the two primitive neuroepitheliomas yielded strong hybridization signals with CCK-specific probes. The five other neuronal tumors were negative for CCK mRNA. The two primitive neuroepitheliomas also synthesized substantial quantities of material reactive in the CCK carboxy-terminal extension RIA system. One of the tumors, Sk-N-Mc, postranslationally processed the CCK prohormonal material poorly, yielding only high mol wt CCK precursors and no immunoreactive CCK. The other, SK-PN-Dw, was able to process the prohormone, producing immunoreactive CCK-like material plus a peptide that immunochemically and chromatographically resembled the intact CCK C-terminal extension peptide. These cultured tumor lines should prove useful in furthering our understanding of the regulation of the CCK gene in human neuronal cells and will also provide an in vitro system for investigation of the posttranslational processing of the CCK preprohormone. In addition, the data demonstrate that screening procedures for examining peptide hormone expression by tumors are most comprehensive when specific molecular genetic probes are employed in addition to standard peptide assay methodology. Finally, these data suggest that CCK production may be a feature of some primitive neuroepitheliomas.

Animals↗

PubMed2003

Malignant peripheral primitive neuroectodermal tumor-peripheral neuroepithelioma of the head and neck: a clinicopathologic study of five cases and review of the literature.

BACKGROUND: The term primitive neuroectodermal tumor (PNET) encompasses a number of neoplasms of common neuroectodermal origin, but of variable clinical, histopathologic, ultrastructural, and molecular characteristics. Here, we focus on one particular member of the PNET family, the malignant peripheral PNET (pPNET) or peripheral neuroepithelioma of head and neck. METHODS: Five patients diagnosed with malignant pPNET-peripheral neuroepithelioma of head and neck were included in the study. All existing literature was reviewed. RESULTS: The diagnosis of malignant pPNET-peripheral neuroepithelioma of the head and neck was confirmed in all five cases. All patients are alive after treatment with a combination of therapeutic modalities; only one patient had metastatic disease develop. A literature review revealed another 38 reported cases. CONCLUSIONS: Malignant pPNET-peripheral neuroepithelioma should be included in the differential diagnosis of small, round, blue cell tumors of head and neck. A combination of multiple diagnostic modalities is essential for correct diagnosis, and multimodality treatment offers the best outcome.

12E7 Antigen↗

PubMed2004

Constitutive activation of the neuregulin-1/erbB signaling pathway promotes the proliferation of a human peripheral neuroepithelioma cell line.

Neuregulin-1 (NRG-1) proteins, acting through their erbB receptors, promote the differentiation, survival and/or proliferation of many cell types in the developing nervous system, including neural crest cells and neural crest-derived Schwann cells. We have recently found that the proliferation of a neoplastic Schwann cell line is dependent on constitutive activation of the NRG-1/erbB signaling pathway and that overexpression of NRG-1 in myelinating Schwann cells induces the formation of malignant peripheral nerve sheath tumors. These observations suggested that NRG-1 might similarly promote mitogenesis in a variety of neural neoplasms including peripheral neuroepitheliomas, aggressive neural crest-derived neoplasms that arise in nerves and soft tissues. To test this hypothesis, we examined the expression of NRG-1 and its erbB receptors in SK-N-MC neuroepithelioma cells. SK-N-MC cells expressed multiple NRG-1 proteins and mRNAs encoding several alpha and beta isoforms from the sensory and motor neuron-derived factor NRG-1 subfamily as well as the NRG-1 receptor subunits erbB2, erbB3, and erbB4. The erbB receptors expressed by SK-N-MC cells were constitutively tyrosine phosphorylated and inhibiting these kinases with the erbB specific inhibitor PD158780 reduced SK-N-MC DNA synthesis in a dose-dependent manner. We conclude that constitutive activation of the NRG-1/erbB signaling pathway promotes the proliferation of SK-N-MC neuroepithelioma cells in vitro and hypothesize that NRG-1/erbB autocrine, paracrine or juxtacrine signaling may contribute to the development and/or progression of neuroepitheliomas in vivo.

Cell Division↗

PubMed2006

Olfactory neuroepithelioma: an immunohistochemical and ultrastructural study.

Three cases of olfactory neuroepithelioma are presented in this report. Histologically, these tumors were composed of small cells with round to oval, relatively hyperchromatic nuclei and scanty cytoplasm. The tumor cells were occasionally observed in tubular formations or rosette-like arrangements. Immunohistochemically, the tumor cells showed a positive reaction for cytokeratin AE1, cytokeratin CAM5.2, Ber-EP4, antisynaptophysin and anti-S100 protein in all cases. In two cases, LH-RH was detected in the tumor cells. Ultrastructurally, the tumor cells had the differentiation features of olfactory epithelium. Olfactory neuroepithelioma is a rare occurrence and it can be very difficult to distinguish olfactory neuroepithelioma from small cell carcinoma, neuroendocrine carcinoma and so-called "olfactory neuroblastoma" on the basis of hematoxylin and eosin stained sections alone. In controversial cases, a diagnosis of olfactory neuroepithelioma must be substantiated by ultrastructural and immunohistochemical findings, particularly regarding the detection of Ber-EP4 and LH-RH immunoreactivity.

Adolescent↗

PubMed1987

Immunohistochemical demonstration of keratin in canine neuroepithelioma.

Morphological features and immunoreactivity for cytokeratin (CK), glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE) of three canine neuroepitheliomas and three canine ependymomas were investigated. Neuroepitheliomas were in three German shepherds as intradural-extramedullary solitary masses, with spinal cord displacement between T10 and L2. Histologically, they contained tubules and acini, lined by epithelial cells with focal squamous metaplasia, rosette-like structures, and polygonal to spindle-shaped cells between tubules. Acini were empty or filled with a homogeneous, eosinophilic periodic acid-Schiff (PAS)-positive material. Mitotic indices varied from low to moderate. Ependymomas occurred in the third (two cases) and fourth ventricle in adult boxers. Histologically, they were composed of cells with an ill-defined, scant amphophilic cytoplasm, with a central round euchromatic nucleus; cells formed pseudorosettes, with a central fibro-vascular stroma. Neuroepitheliomas stained for CK, but ependymomas did not. Both failed to stain for GFAP, NSE, or phosphotungstic acid hematoxylin (PTAH). Thus, antibodies to cytokeratin are useful to distinguish neuroepitheliomas from ependymomas.

Animals↗

PubMed1993

Peripheral neuroepithelioma of the soft tissues. A retrospective analysis of fifteen pediatric patients.

PURPOSE: The purpose of this study was to determine the clinical outcome for pediatric patients with peripheral neuroepithelioma treated with combined modality therapy and followed long enough to account for late relapses. PATIENTS AND METHODS: Fifteen patients, ages 3 3/12 to 19 10/12 years, with peripheral neuroepithelioma (median follow-up 91 months) were diagnosed at The Children's Hospital, Denver, Colorado over the period 1980-1989. All of these malignancies originated in the soft tissues. A critical review of these cases was performed with particular consideration given to the site and stage of the tumor and to the radiographic findings at presentation. Thirteen patients had bulk (> 5 cm in the greatest dimension) or metastatic disease. Four patients had primary tumors involving the chest wall. All patients received chemotherapy, which included at least doxorubicin, vincristine, and cyclophosphamide. Definitive surgical resections were performed on 13 of 15 patients. RESULTS: Five patients relapsed. Three were late relapses 24-44 months after diagnosis. Three of the five patients who relapsed had chest wall primaries. There were three deaths in this series due to peripheral neuroepithelioma and one due to sepsis. The overall survival was 68.5%, and the recurrence-free, survival 55.2%. Two patients with pulmonary relapses were treated with surgery and intensive chemotherapy and remain free of disease > 51 months following recurrence. CONCLUSIONS: Combined treatment modalities appear to be important for optimal outcome. This series represents the first report of favorable outcome of peripheral neuroepithelioma using a series with follow-up that is long enough to account for late relapses.

Adolescent↗

PubMed1993

Human FLI-1 localizes to chromosome 11Q24 and has an aberrant transcript in neuroepithelioma.

The v-ets oncogene family shares a conserved motif, termed the ETS-domain, that mediates sequence-specific DNA binding. This motif is unique among transcription factor families. Using partially degenerate oligonucleotides to highly conserved amino acids in this motif as primers for the polymerase chain reaction, a novel ETS-domain cDNA fragment was generated. This fragment was subsequently used to clone both mouse and human full length cDNAs for this gene. The amino acid sequence of the longest open reading frame showed that this gene was homologous to the mouse FLI-I gene, an ETS family gene activated by Friend erythroleukemia virus insertion. The gene is normally expressed only in hematopoietic cells. The gene was localized to chromosome 11q24, a region of aberrations in Ewing's sarcoma and neuroepithelioma. In the neuroepithelioma cell line TC-32 the FLI-1 transcript is present but has an aberrant structure, indicating that it may be rearranged in neuroepithelioma.

Amino Acid Sequence↗

PubMed1995

Peripheral neuroepithelioma of the kidney.

Peripheral neuroepithelioma is a rare tumor, comprising less than 1% of all soft tissue malignancies arising from the peripheral nonautonomic nervous system. Most peripheral neuroepitheliomas reported were located in the extremities, thoraco-pulmonary region, and pelvic areas, and as many as 30% of cases were associated with peripheral nerve. We report one case of peripheral neuroepithelioma arising in the kidney, mimicking renal cell carcinoma on the CT scan.

Adult↗

PubMed1990

Nerve growth factor-induced differentiation of human neuroblastoma and neuroepithelioma cell lines.

A series of neuroepithelioma and neuroblastoma cell lines were screened for nerve growth factor (NGF)-induced differentiation. All three neuroepithelioma cell lines and all nine neuroblastoma cell lines with amplified N-myc oncogene did not show any apparent NGF-induced differentiation. However, neurite extension was observed for three of six neuroblastoma cell lines with single-copy N-myc oncogene. The three responsive lines had a neuronal phenotype (short processes) which was enhanced by the addition of NGF. The three nonresponsive cell lines were flat without any processes. The addition of NGF to the responsive cell lines resulted in an up-regulation of neurofilament mRNA expression. Peripherin and synapsin, two markers of terminal neuronal differentiation, were not induced. There was little effect of NGF on the rate of cell growth or colony formation on soft agar. Binding of NGF to eight of the cell lines was analyzed by the method of Scatchard. Two responsive neuroblastoma cell lines and one nonresponsive neuroepithelioma cell line expressed both low- and high-affinity binding sites. Two nonresponsive neuroblastoma cell lines expressed only a small number of high-affinity binding sites, and two other nonresponsive neuroblastoma cell lines did not detectably bind NGF. Hence, NGF-induced differentiation is confined to a particular class of neural-related tumors, and, even for these cell lines, differentiation is incomplete.

Cell Differentiation↗

PubMed1987

[Peripheral neuroepithelioma in the retroperitoneum; a case report and a review of the literature].

A 30-year-old man with peripheral neuroepithelioma which was present in the retroperitoneum underwent surgical treatment under the diagnosis of germ cell tumor. Subsequently he died of local recurrence and multiple metastases to the liver seven months after surgery. To our knowledge, this is the second case of peripheral neuroepithelioma which was observed in the retroperitoneal space in the literature of the world. We also reviewed 20 cases of peripheral neuroepithelioma reported in Japan.

Adult↗

PubMedDate not supplied

Peripheral neuroepithelioma developing in the abdominal cavity.

Peripheral neuroepitheliomas are rare malignant tumors of presumed neural crest origin, arising outside the central and sympathetic nervous system. We present herein a case of a young man with diffuse peripheral neuroepithelioma of the abdominal cavity. Although we twice attempted a debulking procedure on this patient, and treated him with alternating VIP-CAV combined chemotherapy, his disease showed a relentless course without responding to any treatment. The development of peripheral neuroepithelioma in the abdominal cavity is an extremely rare occurrence. These rare malignant tumors, of presumed neural crest origin, arise outside the central and sympathetic nervous systems (1). Other names for this tumor are: extracranial primitive neuroectodermal tumor (PNET), Askin tumor, peripheral or adult neuroblastoma (2,3,4). We present a case of a young man with diffuse development of this tumor in the abdominal cavity.

Abdominal Neoplasms↗

PubMed1981

Neuroepithelioma--a rare malignant peripheral nerve tumor of primitive origin: report of two new cases and a review of the literature.

Two cases of primitive neuroectodermal primary peripheral nerve tumors (neuroepitheliomas) are presented. They both demonstrated the rosette pattern described by Homer Wright indicating their neuroectodermal origin, and were unlike Schwann cell tumors. In one case, intensive chemotherapy with local radiotherapy had resulted in a disease-free interval of 30 months at the time of this report. These cases support the existence of neuroepithelioma as a distinct tumor type.

Adult↗

PubMed1990

t(11;22) in three cases of peripheral neuroepithelioma.

Short-term cultures of three cases of peripheral neuroepitheliomas were studied using G-banding technique. A t(11;22)(q24;q12) was recognized in all three tumors. The results strengthen the hypothesis of a common histogenesis for neuroepithelioma, Ewing's sarcoma, and the Askin tumor.

Adolescent↗

PubMed1982

Congenital primitive neuroectodermal tumor (neuroepithelioma) of the chest wall.

Primitive neuroectodermal tumor (neuroepithelioma) is a relatively common central nervous system tumor in children. Those arising from a peripheral nerve are extremely rare in childhood. There is only one reported case in 6-year-old where the tumor arose from the sciatic nerve. A case of neuroectodermal tumor of the chest wall, arising from the intercostal nerve, in a newborn is presented. The tumor metastasized to the brain. Prominent Homer-Wright rosettes, with central eosinophilic fibrillar substance similar to that seen in neuroepithelioma of the central nervous system, were present in the primary tumor and brain metastases. Ultrastructure, as revealed by transmission electron microscopy, is also described.

Brain Neoplasms↗

PubMed1991

Case report 682. Neuroepithelioma of soft tissues of the knee.

Peripheral neuroepitheliomas should be included in the differential diagnosis of a soft-tissue tumor in the extremities or chest wall, especially in young adolescents. MRI provides useful information as to the extent of the tumor and relationship with adjacent structures, although it may not differentiate neuroepitheliomas from other, more common, soft-tissue sarcomas. Together with clinical and histological findings, MRI can assist in the diagnosis and treatment planning of this tumor.

Adolescent↗

PubMedDate not supplied

Peripheral neuroepithelioma with ganglion cells: report of two cases and review of the literature.

Peripheral neuroepitheliomas, also known as peripheral primitive neuroectodermal tumors, are by definition primitive embryonal lesions generally composed of poorly differentiated neuroectodermal elements. We have examined two cases that paradoxically contain extensive foci of ganglionic differentiation similar to that of ganglioneuroblastoma, in addition to primitive elements. One tumor arose from the chest wall of an 8-year-old male and the other from the abdominal wall of a 15-year-old male. Differentiation into a mature ganglionic phenotype was confirmed by immunohistochemistry in one case. Rare peripheral neuroepitheliomas have a capacity for maturation that is not generally appreciated. These lesions should not be confused with ganglioneuroblastomas, which are genotypically unrelated neoplasms.

Adolescent↗

PubMed1987

Translocation of c-sis protooncogene in peripheral neuroepithelioma.

Molecular genetic analysis of the c-sis protooncogene was performed on two neuroepithelioma cell lines carrying a t(11;22)(q24;q12). The c-sis protooncogene was found by in situ hybridization to be translocated from its germline position on chromosome #22 to the derivative chromosome #11 in each cell line. However, it was not rearranged or amplified in either cell line examined. In addition, we did not detect c-sis transcripts in Northern blots of poly (A)+ RNA. This is similar to results found in Ewing's sarcoma, which carries a cytogenetically indistinguishable translocation from neuroepithelioma.

Adolescent↗