Clinical and survival covariates of eight classes of childhood supratentorial neuroglial tumors. (33/337)

BACKGROUND: In the current study, the authors investigated clinical, surgical, and histologic characteristics (covariates) and their interactions in eight previously identified classes of childhood supratentorial neuroglial tumors. The classes resulted from 5 factor score profiles on 703 supratentorial neuroglial tumors in the Childhood Brain Tumor Consortium database. METHODS: The Cox proportional models were used to identify class survival covariates. RESULTS: Age was found to be a survival covariate only in Class 1, in which older age increased the 5-year survival rate 73% from the first year (0.49) to the tenth year (0.85). A greater amount of tumor removed improved survival in Classes 2 and 4 only. Rosenthal fibers improved survival in Class 2 and overrode the negative effects of high Proliferative factor scores and pleomorphic nuclei. Survival for Class 3 children with high Proliferative factor scores improved from 0.60 to 0.95 as the Spongy factor scores increased. Survival in Class 4 increased from 0.17 to 0.39 with total tumor removal. Irregular nuclei and glomeruloid capillaries improved survival in Class 5 patients. Class 6 survival improved with low cell density. Macrocysts in tumors in Classes 1 and 5 were found to improve survival. CONCLUSIONS: As a result of the current study, the authors conclude that survival covariates differ with tumor class and may modify prognosis considerably.  (+info)

MRI findings in a case of a superficial siderosis associated with an ependymoma. (34/337)

We present the imaging findings of superficial siderosis of the central nervous system associated with an ependymoma of the posterior fossa in a patient who presented with progressive bilateral sensorineural hearing loss and cerebellar ataxia. The ependymoma was a homogeneous well-defined mass of the fourth ventricle without hydrocephalus. Secondary siderosis due to chronic bleeding from the ependymoma appeared as linear hypointensity delineating the surface of the cortex, thin and subtle on spin-echo T2-weighted images, thick and obvious on gradient-echo T2-weighted images.  (+info)

ERBB receptor signaling promotes ependymoma cell proliferation and represents a potential novel therapeutic target for this disease. (35/337)

PURPOSE: This study was designed to investigate the biological and therapeutic significance of ERBB1, ERBB2, ERBB3, and ERBB4 in childhood ependymoma. EXPERIMENTAL DESIGN: The expression frequency and clinical significance of ERBB1-4 was analyzed in a large cohort of pediatric ependymoma (n = 121) using immunohistochemistry, Western blotting, and reverse transcription-PCR analysis. Histological markers of anaplasia (necrosis, microvascular proliferation, and Ki-67 proliferative index) were also determined. Functional assessment of ERBB-dependent cell signaling and proliferation, in addition to novel therapeutic inhibition of these processes, was conducted using short-term cultures of human ependymoma cells. RESULTS: Coexpression of ERBB2 and ERBB4 was identified in over 75% of tumors. High-level coexpression of these receptors was significantly related to tumor proliferative activity [P < 0.05; Ki-67 labeling index (LI)] and, in combined survival analysis of clinical (degree of surgical resection) and molecular (ERBB2/ERBB4 expression status and Ki-67 LI) factors, enabled a greater resolution of patient prognosis than any individual variable alone. Ligand-dependent activation of ERBB receptor-signaling in cultured ependymoma cells resulted in AKT phosphorylation and cellular proliferation that was significantly blocked in a dose-dependent manner using WAY-177820, a novel inhibitor of ERBB2 tyrosine kinase activity. CONCLUSIONS: This study suggests that ERBB receptor signaling results in aggressive disease behavior in ependymoma by promoting tumor cell proliferation. An analysis of ERBB2 and ERBB4 expression, in association with Ki-67 LI and the degree of surgical resection, may provide an accurate tool for assessing disease risk in children with this disease. In addition, these receptors may serve as a target for novel therapeutic approaches in ependymoma.  (+info)

Expression of Bcl2 proto-oncogene in primary tumors of the central nervous system. (36/337)

The present study was addressed to find out the expression of Bcl2 proto-oncogene in tumor tissues derived from 25 patients with primary central nervous system tumors. Brain parenchyma in 8 cases, with deeply located tumor, was also examined for Bcl2 expression which served as control. Both benign and malignant tumors (confirmed by histopathological examination) expressed Bcl2 gene product. Tumors exhibited 2-6 fold increase in Bcl2 expression as compared to the normal parenchyma adjacent to some of these tumors studied. However, no correlation was found between the histopathological types of tumor, glial fibrillary acidic protein positivity and degree of Bcl2 expression. Based on this study, we propose that the overexpression of Bcl2 gene product found in primary CNS tumors may be an important molecular event which is known to make the various types of tumor resistant to chemotherapy or radiotherapy.  (+info)

Genomic imbalances in pediatric intracranial ependymomas define clinically relevant groups. (37/337)

The outcome of pediatric ependymomas is difficult to predict based on clinical and histological parameters. To address this issue, we have performed a comparative genomic hybridization screen of 42 primary and 11 recurrent pediatric ependymomas and correlated the genetic findings with clinical outcome. Three distinct genetic patterns were identified in the primary tumors and confirmed by hierarchical cluster analysis. The first group of structural tumors, showed few, mainly partial imbalances (n = 19). A second numerical group showed 13 or more chromosome imbalances with a nonrandom pattern of whole chromosome gains and losses (n = 5). The remaining tumors (n = 18) showed a balanced genetic profile that was significantly associated with a younger age at diagnosis (P < 0.0001), suggesting that ependymomas arising in infants are biologically distinct from those occurring in older children. Multivariate analysis showed that the structural group had a significantly worse outcome compared to tumors with a numerical (P = 0.05) or balanced profile (P = 0.02). Moreover genetic group and extent of surgical resection contributed significantly to outcome whereas histopathology, age, and other clinical parameters did not. We conclude that patterns of genetic imbalances in pediatric intracranial ependymomas may help to predict clinical outcome.  (+info)

Intracranial and spinal ependymomas: review of MR images in 61 patients. (38/337)

OBJECTIVE: To compare the age distribution and characteristic MR imaging findings of ependymoma for each typical location within the neuraxis. MATERIALS AND METHODS: During a recent eleven-year period, MR images of 61 patients with histologically proven ependymomas were obtained and retrospectively reviewed in terms of incidence, peak age, location, size, signal intensity, the presence or absence of cyst and hemorrhage, enhancement pattern, and other associated findings. RESULTS: Among the 61 patients, tumor location was spinal in 35 (57%), infrartentorial in 19 (31%), and supratentorial in seven (12%). In four of these seven, the tumor was located in brain parenchyma, and in most cases developed between the third and fifth decade. Approximately half of the infratentorial tumors occurred during the first decade. The signal intensity of ependymomas was nonspecific, regardless of their location. A cystic component was seen in 71% (5/7) of supratentorial, 74% (14/19) of infratentorial, and 14% (5/35) of spinal cord tumors. Forty- nine percent (17/35) of those in the spinal cord were associated with rostral and/or caudal reactive cysts. Intratumoral hemorrhage occurred in 57% (4/7) of supratentorial, 32% (6/19) of infratentorial, and 9% (3/35) of spinal cord tumors. In 17% (6/35) of spinal ependymomas, a curvilinear low T2 signal, suggesting marginal hemorrhage, was seen at the upper and/or lower margins of the tumors. Peritumoral edema occurred in 57% (4/7) of supratentorial, 6% (3/19) of infratentorial and 23% (8/35) of spinal cord tumors. Seventy-two percent (5/7) of supratentorial and 95% (18/19) of infratentorial tumors showed heterogeneous enhancement, while in 50% (17/34) of spinal cord tumors, enhancement was homogeneous. CONCLUSION: Even though the MR imaging findings of ependymomas vary and are nonspecific, awareness of these findings, and of tumor distribution according to age, is helpful and increases the likelihood of correct preoperative clinical diagnosis.  (+info)

Transplantation resistance to mouse ependymoblastoma following immunization with dehistonized syngeneic tumor chromatin. (39/337)

Female C57BL/J6 mice pretreated with dehistonized ependymoblastoma chromatin rejected 5 x 10(4) or 10(5) s.c.-implanted syngeneic ependymoblastoma cells. Control mice that received Freund's adjuvant containing dehistonized chromatin from normal mouse brain developed palpable tumor nodules in 90% and 35 to 45% of the animals, respectively. Increased binding of spleen lymphocytes from mice pretreated with dehistonized tumor chromatin to Sepharose 4B coupled with components of dehistonized tumor chromatin was observed. This provides initial evidence for the presence of "committed" lymphocytes in mice pretreated with dehistonized chromatin from this mouse ependymoblastoma.  (+info)

Prolonged tumor dormancy by prevention of neovascularization in the vitreous. (40/337)

Tumors release a diffusible substance that stimulates neovascularization. To study the neovascularization that occurs in diabetic retinopathy, we implanted V2 carcinomas and mouse ependymoblastomas into the vitreous of experimental animals. In the vitreous, unlike previous sites, the tumors failed to stimulate neovascularization. They grew for weeks as small, unvascularized, three-dimensional aggregates of cells. Explosive growth into a large, vascularized mass occurred when the avascular tumors reached the retinal surface. The vitreous proved to be a valuable model for observing the in vivo growth of small, solid tumors. Xenografts survived for months without evidence of immune rejection. The consequence of the prolonged avascular state is the restriction of tumor size. The normal vitreous may act to inhibit capillary proliferation. An understanding of the mechanism for maintaining the avascular state may lead to therapeutic blockade of neovascularization. This would be important in the management of diabetic retinopathy and neoplasia.  (+info)