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PubMed2002

Influence of tumor grade on time to progression after irradiation for localized ependymoma in children.

PURPOSE: To investigate the influence of histologic grade on progression-free survival (PFS) after irradiation (RT) for pediatric patients with localized ependymoma. METHODS AND MATERIALS: Fifty patients with localized ependymoma (median age 3.6 years, range 1-18 years at the time of RT) were treated with RT between December 1982 and June 1999. Anaplastic features were identified in 14 of 50 patients. The extent of resection was characterized as gross-total in 36 patients, near-total in 5, and subtotal in 9. The median dose to the primary site was 54 Gy. Of the 50 patients, 23 received pre-RT chemotherapy. RESULTS: Thirty-nine patients were alive at a median follow-up of 46 months (range 21-214) from diagnosis. Thirty-four patients remained progression free at a median follow-up of 35 months (range 13-183) after the initiation of RT. Progression occurred in 16 patients (12 local and 4 local and distant), with a median time to failure of 21.2 months (range 4.6-65.0). The tumor grade significantly influenced the PFS after RT (p < 0.0005). The estimated 3-year PFS rate was 28% +/- 14% for patients with anaplastic ependymoma compared with 84% +/- 8% for patients with differentiated ependymoma. These results remained significant when corrected for age at diagnosis (<3 years), pre-RT chemotherapy, and extent of resection. Patients who received pre-RT chemotherapy had an inferior 3-year PFS estimate after RT (49 +/- 12%) compared with those who did not (84% +/- 10%; p = 0.056). Anaplastic ependymoma was found more frequently in the supratentorial brain (p = 0.002). Six of 12 patients with supratentorial tumor developed recurrence; recurrence was restricted to patients with anaplastic ependymoma. CONCLUSION: Tumor grade influences outcome for patients with ependymoma independent of other factors and should be considered in the design and analysis of prospective trials involving pediatric patients treated with RT. Chemotherapy before RT influences the PFS and overall survival after RT. The effect is more pronounced when progression occurs during chemotherapy.

Adolescent↗
PubMed1998

Primary ependymoma of the mediastinum: a clinicopathologic study of three cases.

Primary mediastinal ependymomas are unusual tumors, with only two case reports previously reported in the literature. In this study, we review our experience with three cases of primary mediastinal ependymomas, including the clinical, histopathologic, immunohistochemical, and ultrastructural features. The three patients in this study were white women with a mean age of 50 years (age range, 36 to 71 years). Presenting symptoms were nonspecific; radiographically, all lesions were circumscribed posterior mediastinal masses without evidence of bone involvement. There was no evidence of central nervous system, sacral, or pelvic ependymoma. All tumors were completely resected, ranged in size from 5 to 7 cm (mean, 6 cm), and exhibited glistening pseudocapsules. Two tumors had a solid, tan-gray cut surface and one lesion was cystic with a mural tumor nodule. All neoplasms showed histologic features of conventional cellular ependymomas with perivascular pseudorosettes and occasional true ependymal rosettes. Germ cell components were not present in any case and immunohistochemical analysis showed glial fibrillary acidic protein, S-100, and patchy cytokeratin immunoreactivity in all three cases as well as absence of reactivity for HMB 45, chromogranin, and synaptophysin. Ultrastructural features included multipart "zipper-like" junctions, intracytoplasmic lumina containing microvilli, occasional cytoplasmic basal bodies, and apical cilia. A microscopic metastasis was present in a regional lymph node in one case at the time of resection; however, there is no evidence of recurrence or distant metastasis in any of the cases during the postoperative period (mean length of follow-up, 64 months). Ependymomas rarely occur in the mediastinum and have a predilection for the posterior mediastinum. The paravertebral location, microscopic identification of adjacent sympathetic ganglia, and lack of teratomatous or other germ cell components suggest that mediastinal ependymomas are likely derived from paravertebral ependymal rests. Primary mediastinal ependymomas are characterized by a prolonged and indolent clinical course. Metastasis to regional lymph nodes may occur, but distant metastases are unusual in our experience. Complete surgical excision seems to offer the best chance for long-term survival.

Adult↗
PubMed1999

Evidence for an ependymoma tumour suppressor gene in chromosome region 22pter-22q11.2.

Ependymomas are glial tumours of the brain and spinal cord. The most frequent genetic change in sporadic ependymoma is monosomy 22, suggesting the presence of an ependymoma tumour suppressor gene on that chromosome. Clustering of ependymomas has been reported to occur in some families. From an earlier study in a family in which four cousins developed an ependymoma, we concluded that an ependymoma-susceptibility gene, which is not the NF2 gene in 22q12, might be located on chromosome 22. To localize that gene, we performed a segregation analysis with chromosome 22 markers in this family. This analysis revealed that the susceptibility gene may be located proximal to marker D22S941 in 22pter-22q11.2. Comparative genomic hybridization showed that monosomy 22 was the sole detectable genetic aberration in the tumour of one of the patients. Loss of heterozygosity studies in that tumour revealed that, in accordance to Knudson's two-hit theory of tumorigenesis, the lost chromosome 22 originated from the parent presumed to have contributed the wild-type allele of the susceptibility gene. Thus, our segregation and tumour studies collectively indicate that an ependymoma tumour suppressor gene may be present in region 22pter-22q11.2.

Central Nervous System Neoplasms↗
PubMed1999

Results of microsurgical treatment for intramedullary spinal cord ependymomas: analysis of 36 cases.

OBJECTIVE: Although intramedullary spinal cord ependymomas are amenable to surgical total resection, some ependymomas have been associated with severe surgical morbidity. The aim of this study is to determine what factors affect surgical morbidity. METHODS: Thirty-six consecutive patients who underwent surgical removal of an intramedullary spinal cord ependymoma between September 1980 and June 1998 were studied retrospectively. This series includes 19 women and 17 men between the age of 12 and 67 years (mean age, 41.2 yr). The location of the tumors was cervical in 24 cases, cervicothoracic in 3 cases, thoracic in 7 cases, and conus in 2 cases. At surgery, complete removal was achieved in 34 patients and subtotal removal was performed in the remaining 2. RESULTS: There has been no tumor recurrence in any patient except one who had an anaplastic ependymoma after a mean follow-up period of 56 months. The surgery improved neurological status in 14 of the 36 patients (39%). However, five patients (14%) experienced persistent deteriorations in clinical grade caused by surgery. Four of the five patients harbored benign ependymomas in the thoracic cord and characteristically demonstrated arachnoid scarring and cord atrophy at surgery, indicating that tumors had been present for a long time. CONCLUSION: Surgical removal of intramedullary ependymomas is beneficial to patients. However, the thoracic cord may be susceptible to surgical manipulations for intramedullary ependymomas. In addition, intraoperative findings of arachnoid scarring and cord atrophy are ominous for surgical morbidity.

Adolescent↗
PubMed2000

The immunophenotype of ependymomas.

The morphologic distinction of ependymomas with epithelial cytology from metastatic carcinoma may pose a significant problem in differential diagnosis. The known presence of keratin in glioma cells further complicates the issue. Using the labeled streptavidin-biotin method with automated staining, we studied epithelial and glial marker expression in 52 ependymomas of varying type and grade, including 20 epithelial-appearing, 14 glial-appearing, eight mixed pattern, and 10 myxopapillary tumors; 38 were low grade and 14 anaplastic. All tumors were immunoreactive for glial fibrillary acidic protein (GFAP), and S-100 protein. Diffuse staining for GFAP was noted in glial-appearing ependymomas featuring perivascular pseudorosettes. Diffuse immunostaining for S-100 protein was seen in cellular lesions exhibiting epithelial-like features. Staining was more diffuse for GFAP than S-100 protein in anaplastic ependymomas. Keratin (AE1/AE3) reactivity was seen in 98% of cases, the pattern being similar to that of GFAP. The frequency of staining for other keratins varied: wide-spectrum keratin (35%), cytokeratin (CK)7 (20%), CAM 5.2 (19%), CK903 (14%), and CK20 (8%); as a rule, it was scant and limited to occasional cells and processes. epithelial membrane antigen (EMA) staining was seen in 36% of all cases and in 67% of epithelial-appearing tumors wherein it often high-lighted microlumina. Aside from AE1/AE3 staining and very infrequent wide-spectrum keratin and EMA reactivity, expression of epithelial markers was not seen in anaplastic ependymomas. No carcinoembryonic antigen (CEA) positivity was noted in any case. Collagen IV reactivity was limited to tumor cell-stroma interfaces. Although variable, S-100 protein and GFAP staining is seen in all ependymomas, particularly in true and perivascular pseudorosettes. Widespread reactivity for keratin AE1/AE3 corresponds closely to the pattern of GFAP staining. Significant staining for other keratins or for CEA is inconsistent with a diagnosis of ependymoma. EMA reactivity is largely limited to luminal staining of rosettes and tubules.

Biomarkers, Tumor↗
PubMed1996

Expression of platelet-derived growth factor transcripts in medulloblastomas and ependymomas.

We used Northern blot analysis to measure the expression of mRNA for platelet-derived growth factor subunit A (PDGF-A), PDGF-B and the PDGF-alpha receptor (PDGFR-alpha) and PDGF-beta receptor (PDGFR-beta) in ependymomas and medulloblastomas. We analyzed tissue from 5 patients for each tumor type, looking specifically for components of an autocrine or paracrine system in these tumors. PDGF-A was expressed in all tumors, PDGFR-alpha, which binds all 3 PDGF isoforms, was only found in ependymomas. Thus only ependymomas appeared to have a potential for using PDGFR-alpha autocrine loops. PDGF-B was expressed only in ependymomas, although the PDGFR-beta was expressed in both medulloblastomas and ependymomas. Again, therefore, only ependymomas appear to have a potential autocrine loop with PDGFR-beta. These data suggest that ependymomas have the biochemical prerequisites for autocrine and/or paracrine loops using PDGFR-alpha or PDGFR-beta systems. In this they resemble other glial tumors such as anaplastic astrocytomas and glioblastomas. Medulloblastomas do not appear to have the ligand and/or receptor for either the PDGFR-alpha or PDGFR-beta autocrine loop.

Blotting, Northern↗
PubMed2005

Supratentorial cortical ependymoma: report of three cases.

OBJECTIVE AND IMPORTANCE: Extraventricular ependymomas account for 50% of supratentorial ependymomas. Some tumors may extend to the gray matter reaching the pial surface, but pure cortical ependymomas are uncommon. Here, we report three patients with supratentorial intracortical ependymoma. CLINICAL PRESENTATION: We reviewed the clinicopathological findings of all patients operated on for ependymomas at the Bellaria Hospital during an 11-year period and found three lesions described as cortical ependymomas. The three lesions represented 2.5% of all ependymal tumors and 21.4% of supratentorial tumors operated on during the study period. The patient were aged 52, 24, and 11 years (mean, 32.3 yr). One was female. All presented with seizures. On imaging, the lesions were confined to the gray matter, were solid, and demonstrated diffuse enhancement. INTERVENTION: Gross total resection was achieved in all instances. Two patients were treated with surgery, and one was treated with surgery and postoperative radiotherapy. All tumors were low grade. After a mean follow-up of 92.6 months, no patient had recurrence or leptomeningeal dissemination. Review of preoperative magnetic resonance imaging scans confirmed an intracortical location. Routine sections were reviewed, and additional immunoreactions for epithelial membrane antigen, glial fibrillary acidic protein, synaptophysin, neurofilament proteins, S-100 protein, and Ki-67 and electron microscopy were performed. CONCLUSION: Cortical ependymomas seem to behave as benign tumors amenable to surgical removal. Local recurrence and leptomeningeal dissemination seem to be unlikely. Postoperative radiotherapy is unnecessary.

Adult↗
PubMed1990

Intracranial ependymoma and subependymoma: MR manifestations.

In order to provide a detailed description of the MR appearance of intracranial ependymoma, the MR examinations of 12 patients (10 with ependymomas and two with subependymomas) were reviewed and correlated with operative and pathologic reports. Three of 10 ependymomas were intraventricular, two were intraparenchymal, and five were transependymal, extending from CSF spaces into parenchyma. Both subependymomas were intraventricular. Solid ependymomas and subependymomas were iso- to hypointense relative to normal white matter on T1-weighted images and hyperintense on proton-density- and T2-weighted images. Foci of signal heterogeneity within solid neoplasms represented methemoglobin, hemosiderin, necrosis, calcification, and encased native vessels or tumor vascularity. Gd-DTPA-enhanced images in two patients differentiated enhancing tumor from surrounding nonenhancing edema and from surrounding normal brain parenchyma. Cystic neoplasms had sharply defined, round or oval margins and uniform signal intensity equivalent to or slightly hyperintense relative to CSF. Tumor-associated calcification was not demonstrated readily by MR. Sagittal and coronal images were valuable in assessing the amount of intraventricular tumor and route of extension. We conclude that the MR differentiation of ependymomas and subependymomas from other gliomas is provided most reliably by the location and morphology of the tumor and not by differences in signal intensity. The typical ependymoma arises within the fourth ventricle as a solid mass with heterogeneous signal intensity. A propensity for spread is seen along the CSF pathways via the foramina of Magendie and Luschka and the aqueduct of Sylvius. Supratentorial ependymomas may be periventricular in location and have cystic components. The two subependymomas in our series were solid, intraventricular tumors with relatively homogeneous signal intensities.

Adolescent↗
PubMed2001

Identification of novel regions of allelic loss in ependymomas by high-resolution allelotyping with 384 microsatellite markers.

OBJECT: Ependymomas are rare glial neoplasms; little is known about the molecular pathogenesis of this tumor entity. In a previous study the authors found multiple genomic imbalances in ependymomas resected in 20 adults and eight children, including loss of chromosomes 1p, 6, 16, 17, 19q, 20q, and 22q, as well as gain of chromosomes 4q, 5q, 7q, 9q, and 12q on comparative genomic hybridization. The aim of this study was to map in more detail the commonly affected regions in ependymomas. METHODS: A comprehensive allelotype analysis of 16 ependymomas was conducted using 384 microsatellite markers that span the 22 autosomes. Based on this high-resolution loss of heterozygosity analysis, multiple overlapping deletion regions were identified as follows: 6q25.2-27, 16p12-13.1, 16q22.3-24.1, 17q22-24, 19q12-13.2, 20q13.2-13.3, and 22q13.1-13.3. CONCLUSIONS: These data confirmed previous reports that loss of chromosomes 17 and 22 were common in ependymomas. Moreover, the authors were able to identify loss of chromosomes 13, 16, 19, and 20 as novel findings in ependymomas. It is believed that potential tumor suppressor genes that reside in these commonly deleted regions may contribute to the molecular tumorigenesis of ependymomas.

Adolescent↗
PubMed2005

Long-term outcome in patients harboring intracranial ependymoma.

OBJECT: The prognostic significance of tumor grade and resection and the efficacy of prophylactic radiation remain controversial in the management of intracranial ependymoma. The outcomes in patients with intracranial ependymoma treated at the Kyoto University Hospital were reviewed retrospectively, and prognostic significance was analyzed. METHODS: Between 1972 and 2002, 29 patients were seen at the authors' institution. Eighteen cases involved a Grade II lesion according to the World Health Organization classification of ependymoma and 11 involved a Grade III lesion. Postoperative radiation was applied in 24 cases and chemotherapy was administered in nine. Overall survival and progression-free survival rates were significantly higher in patients with Grade II ependymoma (p = 0.006 and 0.004, respectively) and in patients who had undergone gross-total resection of the tumor (p = 0.002 and 0.04, respectively). Fourteen patients relapsed from 10 to 120 months (median 39 months) after diagnosis. In nine patients the ependymoma recurred only at the original tumor site. Three patients experienced both local and distant relapse, whereas two others had only a distant relapse. All relapses of the Grade II ependymoma initially occurred at the primary tumor site. Histological grade and extent of resection were significantly associated with tumor dissemination (p = 0.0034 and 0.0011, respectively). The field of postoperative radiation had no impact on patient survival or lesion recurrence. CONCLUSIONS: Tumor grade and resection are the two important prognostic factors with respect to patient survival, tumor recurrence, and tumor dissemination. Considering that relapses were predominantly local and that there was no apparent benefit from prophylactic radiation, the authors concluded that postoperative radiation should be focused on local control, especially for Grade II ependymomas.

Adolescent↗
PubMed2002

Current management of childhood ependymoma.

Radiation therapy has long been a mainstay in the treatment of ependymoma. Concerns about the long-term effects of radiation therapy have made many parents and caregivers wary of this treatment modality. However, with the advent of conformal radiation and evidence supporting its use in younger children (ie, < 3 years old), the standard of care for childhood ependymoma is rapidly evolving to include immediate postoperative radiation therapy for all pediatric patients. The role of chemotherapy in the treatment of ependymoma has diminished recently because (1) chemotherapy fails to delay radiation therapy for a meaningful period of time; (2) tumors that progress during chemotherapy do not respond as well to subsequent irradiation; and (3) the combination of chemotherapy and irradiation does not improve overall survival. However, chemotherapy may make residual tumor more amenable to a second resection. Fewer than 50% of pediatric patients with ependymoma undergo complete resection before receiving radiation therapy. Because the extent of resection is one of the most important prognostic factors in the treatment of this disease, increasing the rate of complete resections is a significant means of increasing long-term survival. By incorporating current concepts of ependymoma, a more uniform approach to the treatment of this disease can be developed. In addition, by combining the best available means of detecting and managing side effects, the future for pediatric patients with ependymoma remains optimistic. This review presents historical and current practices used to treat ependymoma, and is intended to provide an information framework for caregivers so that they can assist parents in the decision-making process.

Adolescent↗
PubMed2004

Overexpression of cyclooxygenase-2 in childhood ependymomas: role of COX-2 inhibitor in growth and multi-drug resistance in vitro.

The management of ependymomas remains one of the most frustrating issues in pediatric neuro-oncology. Gross total resection is not always possible, and intensive chemotherapy and craniospinal radiotherapy have made no clear advances. Moreover, the chemoresistance of ependymomas may be explained by the expression of membrane transport molecule P-glycoprotein (P-gp). In this study the expression of cyclooxygenase 2 (COX-2) and the role of the specific COX-2 inhibitor NS-398 in growth and multi-drug resistance of ependymomas were investigated. COX-2 protein expression was assessed in 19 ependymomas immunohistochemically, and the effect of NS-398 on growth and multi-drug resistance was investigated using two primary cultured ependymoma cell lines. COX-2 protein expression was observed in 15 (79%) of the 19 ependymomas. NS-398 was found to reduce the proliferation of monolayer cell cultures in a dose- and time-dependent manner and to induce apoptosis and lower bcl-2 protein levels. After NS-398 treatment, Western blotting showed reduced P-gp expression and a rhodamine 123 efflux assay demonstrated a significant decrease in P-gp activity. Our findings demonstrate that COX-2 is overexpressed in ependymomas and that NS-398 is able to induce apoptosis and suppress P-gp expression and activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Intracranial ependymoma and subependymoma: MR manifestations.

In order to provide a detailed description of the MR appearance of intracranial ependymoma, the MR examinations of 12 patients (10 with ependymomas and two with subependymomas) were reviewed and correlated with operative and pathologic reports. Three of 10 ependymomas were intraventricular, two were intraparenchymal, and five were transependymal, extending from CSF spaces into parenchyma. Both subependymomas were intraventricular. Solid ependymomas and subependymomas were iso- to hypointense relative to normal white matter on T1-weighted images and hyperintense on proton-density- and T2-weighted images. Foci of signal heterogeneity within solid neoplasms represented methemoglobin, hemosiderin, necrosis, calcification, and encased native vessels or tumor vascularity. Gd-DTPA-enhanced images in two patients differentiated enhancing tumor from surrounding nonenhancing edema and from surrounding normal brain parenchyma. Cystic neoplasms had sharply defined, round or oval margins and uniform signal intensity equivalent to or slightly hyperintense relative to CSF. Tumor-associated calcification was not demonstrated readily by MR. Sagittal and coronal images were valuable in assessing the amount of intraventricular tumor and route of extension. We conclude that the MR differentiation of ependymomas and subependymomas from other gliomas is provided most reliably by the location and morphology of the tumor and not by differences in signal intensity. The typical ependymoma arises within the fourth ventricle as a solid mass with heterogeneous signal intensity. A propensity for spread is seen along the CSF pathways via the foramina of Magendie and Luschka and the aqueduct of Sylvius. Supratentorial ependymomas may be periventricular in location and have cystic components. The two subependymomas in our series were solid, intraventricular tumors with relatively homogeneous signal intensities.

Adult↗
PubMed1984

[Clinical features and CT scan findings of supratentorial ependymomas and ependymoblastomas].

The clinical courses and CT scan findings of 12 cases of supratentorial ependymoma and ependymoblastoma were reviewed. The age of the patient of ependymoma ranged from 3 years to 34 years, with an average age of 16 years. The follow-up time ranged from 2 months to 9 years and 10 months. All of the six patients are still alive. The age of the patients of ependymoblastoma ranged from 7 months to 34 years, with an average age of 17 years. During the follow-up period from 2 weeks to 6 years and 4 months, four patients died. Supratentorial ependymomas and ependymoblastomas show the following characteristic features of CT scans: Calcification: The incidence of calcification was 50% in ependymoma-group, and 100% in ependymoblastoma-group. Cyst formation, ring-enhancement: The cyst formation was noticed in both groups. In ependymoma-group a smooth ring-enhancement pattern and the strongly enhanced mural nodule-like contour were found, but in ependymoblastoma-group, the cyst wall was enhanced in irregular shape. Perifocal edema and mass effect: Considerable mass effect was noticed in both groups. Perifocal edema was slight in many cases of ependymoma-group, but mostly prominent in ependymoblastoma-group. CT scan findings of recurrent tumor: In ependymoma-group, recurrent tumor showed the same characteristics of CT scan as the initial ones. In ependymoblastoma-group, cystic portion decreased in size and irregular shaped solid portion increased in recurrence.

Adolescent↗
PubMed1997

Adjuvant chemotherapy for the treatment of intracranial ependymoma of childhood.

BACKGROUND: Current treatment for childhood intracranial ependymomas with surgery and radiation therapy (RT) yields 5-year survival rates ranging from 50-70% after complete resection to 0-30% after incomplete surgical resection. The role of chemotherapy in the treatment of ependymoma has not been established. In this pilot study, children with newly diagnosed intracranial ependymoma were treated with RT and chemotherapy using agents comparable to those found to be active in the treatment of intracranial ependymoma in infants. METHODS: Nineteen children age 3-14 years (median, 7.5 years) were treated with postoperative RT and chemotherapy. Chemotherapy was comprised of carboplatin, 560 mg/m2, with vincristine, 1.5 mg/m2, weekly for 3 weeks, alternating at 4-week intervals with ifosfamide, 1.8 g/m2, and etoposide, 100 mg/m2, for 5 consecutive days for a total of 4 cycles. RESULTS: The 5-year progression free survival (PFS) estimate was 74%. The extent of surgical resection was not a significant prognostic factor in this study. By contrast, ependymomas located in the posterior fossa were associated with a higher rate of progression (P = 0.036). Toxicity, limited predominantly to myelosuppression, was manageable. CONCLUSIONS: The PFS for children with postoperative residual ependymoma treated with RT and chemotherapy in this study was higher than published survival results for RT alone. These results suggest a role for multialkylator chemotherapy in incompletely resected intracranial ependymoma and provide the rationale for a randomized trial comparing this strategy with conventional postoperative RT.

Adolescent↗
PubMed1988

The proliferative potential of human ependymomas measured by in situ bromodeoxyuridine labeling.

Twelve patients with ependymomas received a 30- to 60-minute intravenous infusion of bromodeoxyuridine (BrdU), 150 to 200 mg/m2 at surgery, to label tumor cells in the DNA synthesis phase. Labeled cells were detected in excised tumor specimens by indirect immunoperoxidase staining using anti-BrdU monoclonal antibody as the first antibody. The BrdU labeling index (LI, defined as the percentage of labeled cells in relation to the total number of cells scored) was calculated for each specimen. All four spinal cord ependymomas had a BrdU LI of less than 1%, which is consistent with our clinical experience that most such tumors grow slowly and have an excellent prognosis. Five of the eight intracranial ependymomas also had a low BrdU LI of approximately 1% or less, and three had a BrdU LI of 3.2%, 3.4%, and 4.8%. The latter three tumors, only one of which was diagnosed as a malignant ependymoma at the time of study, were either recurrent or recurred within 2 years after gross or subtotal removal. Cytologic analysis of cerebrospinal fluid (CSF) was performed in five cases; CSF seeding of tumor cells was found in only one patient, who had a malignant ependymoma. A high BrdU LI did not always correlate with CSF seeding. Measurement of the LI using BrdU and anti-BrdU monoclonal antibodies can provide more accurate information on the proliferative potential of individual tumors and may lead to a more rational grading system of ependymomas. The results of such studies do not always predict the potential for CSF seeding.

Adult↗
PubMed2005

Localization of a putative low-penetrance ependymoma susceptibility locus to 22q11 using a chromosome 22 tiling-path genomic microarray.

Ependymomas frequently display allelic loss of chromosome 22 in the absence of mutations in the known tumor-suppressor genes on chromosome 22, suggesting the role of an alternative predisposing gene or genes from this chromosome. In an effort to localize these genes, 37 ependymomas derived from 33 patients were analyzed for the presence of copy number changes by use of a high-resolution chromosome 22 genomic microarray. Eighteen ependymomas (49%) displayed an array-CGH profile consistent with monosomy of chromosome 22. However, in 10 of these tumors, the fluorescence ratios for 22q clones scored as deleted were different from those at the single gene copy level. This suggests either analysis of mixed populations of tumor and normal stromal cells or analysis of mixed tumor cell populations with different genetic profiles. Four ependymomas derived from two patients showed overlapping interstitial deletions of 2.2 Mb and approximately 510 kb. Further analyses revealed that these deletions were present in the constitutional DNA of these two patients as well as in some of their unaffected relatives. Detailed microsatellite analysis of these families refined the commonly deleted segment to a region of 320 kb between markers RH13801 and D22S419. Our results provide additional evidence for the involvement of genes on chromosome 22 in the development of ependymoma and suggest the presence of a low-penetrance ependymoma susceptibility locus at 22q11.

Adolescent↗
PubMed2004

Analysis of HIC-1 methylation and transcription in human ependymomas.

Ependymomas are among the most common brain tumors in children. They develop from ependymal cells lining the ventricular system of the CNS. Previous studies have demonstrated a significant rate of allelic loss at chromosome 17p13.3. The HIC-1 putative tumor-suppressor gene, which exhibits hypermethylation and loss of expression in various tumor entities including medulloblastomas and gliomas, maps to the affected region. In the present study, we analyzed HIC-1 in ependymomas. Therefore, we applied methylation-specific PCR of the 5'-untranslated region as well as of a central region of HIC-1 and bisulfite sequencing to determine the methylation status in 52 ependymomas of different histologic subtypes, grades and locations. In addition, we used a competitive RT-PCR approach for sensitive assessment of HIC-1 transcripts. Hypermethylation of at least one of the 2 analyzed regions was found in 43/52 (83%) cases. There was a significant correlation between hypermethylation of HIC-1 and nonspinal localization (p = 0.019) as well as age. Of 27 ependymomas, 22 (81%) showed absent or low expression of HIC-1. The elevated methylation of HIC-1 in nonspinal ependymomas supports the hypothesis that spinal and nonspinal ependymomas represent genetically distinct entities.

Adolescent↗