Primary Nervous System Tumors Research Articles

Clinical Findings and Outcome in 30 Dogs with Presumptive or Confirmed Nerve Sheath Tumors.

Nerve sheath tumors (NSTs) are well-recognized primary nervous system tumors, but there is relatively limited information in dogs including comparison of NSTs in different anatomical locations. This retrospective study describes the clinical features and outcomes in a group of dogs with NSTs affecting the cranial nerves or spinal nerves. Thirty dogs were included, 25 with a presumptive diagnosis and five confirmed by histopathologic analysis. Seven dogs also had cytology of tumor samples, which were supportive of the NST diagnosis in four. Eight dogs had cranial nerve-associated NSTs, with six involving the trigeminal nerve. Twenty-two dogs had spinal nerve-associated NSTs including 13 invading the spinal canal and nine peripheral to the spinal canal, with the majority affecting nerves or nerve roots of the brachial plexus. The prognosis was poor, with dogs being euthanized eventually because of disease progression. Among dogs alive 1 week after diagnosis, the median survival time was 4 months but ranged from 2 weeks to >2 years. While there was a broad overlap between NST locations, survival was generally longer for dogs without spinal canal or intracranial involvement. The results expand available information on NSTs in dogs but should be interpreted with caution given the small number of dogs with a definitive diagnosis. Further investigation is warranted to determine how tumor location, invasiveness, and treatments pursued impact outcome.

NIMG-52. CORRELATION OF BIDIMENSIONAL AND VOLUMETRIC TUMOR SIZING IN NEWLY DIAGNOSED AND RECURRENT GLIOBLASTOMA

Abstract BACKGROUND Glioblastoma (GBM) is the most common malignant primary nervous system tumor and remains incurable with a poor prognosis despite current therapy. The standard for monitoring response to treatment, as defined by the Response Assessment in Neuro-Oncology (RANO) criteria, relies on a bidimensional (2D) measurement product of T1-gadolinium enhancing disease. However, due to the variability of bidimensional tumor characterization, there is considerable interest in volumetric segmentation to assess tumor burden, which could be implemented using machine learning models offering workflow automatization. METHODS In this study, we evaluate a commercially available automated tumor segmentation tool and correlate its volumetric output to the manual assessment of bidimensional 2D enhancing tumor burden by experts. MRI examinations during systemic treatment for two retrospective cohorts of patients with either newly diagnosed (nGBM) or recurrent GBM (rGBM) were assessed. The 2D diameter product in cm^2 of enhancing tumor was determined by blinded readers and volumetric segmentations in cm^3 were automatically generated. Spearman's correlation between the manual 2D and automated volume measurements was calculated for each cohort. RESULTS 315 patients with nGBM, and 482 with rGBM were evaluated, comprising 3073 total brain MRIs in the nGBM cohort and 2439 MRIs in the rGBM cohort. Spearman's correlation between the manual 2D and automated volumetric measurements was 0.7463 (0.730, 0.762) in the nGBM cohort and 0.8598 (0.849, 0.870) in the rGBM cohort. CONCLUSION Automated segmentation tools have the potential to revolutionize radiology workflows and increase sensitivity to subtle changes on imaging. However, the differential performance of this volumetric assessment confirms the need for further refinement and customization of such automated tools to account for tumor- and patient-specific factors.

Dynamic Regulation Genes at Microtubule Plus Ends: A Novel Class of Glioma Biomarkers

Glioma is the most prevalent and aggressive primary nervous system tumor with an unfavorable prognosis. Microtubule plus-end-related genes (MPERGs) play critical biological roles in the cell cycle, cell movement, ciliogenesis, and neuronal development by coordinating microtubule assembly and dynamics. This research seeks to systematically explore the oncological characteristics of these genes in microtubule-enriched glioma, focusing on developing a novel MPERG-based prognostic signature to improve the prognosis and provide more treatment options for glioma patients. First, we thoroughly analyzed and identified 45 differentially expressed MPERGs in glioma. Based on these genes, glioma patients were well distinguished into two subgroups with survival and tumor microenvironment infiltration differences. Next, we further screened the independent prognostic genes (CTTNBP2, KIF18A, NAV1, SLAIN2, SRCIN1, TRIO, and TTBK2) using 36 prognostic-related differentially expressed MPERGs to construct a signature with risk stratification and prognostic prediction ability. An increased risk score was related to the malignant progression of glioma. Therefore, we also designed a nomogram model containing clinical factors to facilitate the clinical use of the risk signature. The prediction accuracy of the signature and nomogram model was verified using The Cancer Genome Atlas and Chinese Glioma Genome Atlas datasets. Finally, we examined the connection between the signature and tumor microenvironment. The signature positively correlated with tumor microenvironment infiltration, especially immunoinhibitors and the tumor mutation load, and negatively correlated with microsatellite instability and cancer stemness. More importantly, immune checkpoint blockade treatment and drug sensitivity analyses confirmed that this prognostic signature was helpful in anticipating the effect of immunotherapy and chemotherapy. In conclusion, this research is the first study to define and validate an MPERG-based signature closely associated with the tumor microenvironment as a reliable and independent prognostic biomarker to guide personalized choices of immunotherapy and chemotherapy for glioma patients.

Gene replacement therapy in a schwannoma mouse model of neurofibromatosis type 2

Loss of function of the neurofibromatosis type 2 (NF2) tumor suppressor gene leads to the formation of schwannomas, meningiomas, and ependymomas, comprising ∼50% of all sporadic cases of primary nervous system tumors. NF2 syndrome is an autosomal dominant condition, with bi-allelic inactivation of germline and somatic alleles resulting in loss of function of the encoded protein merlin and activation of mammalian target of rapamycin (mTOR) pathway signaling in NF2-deficient cells. Here we describe a gene replacement approach through direct intratumoral injection of an adeno-associated virus vector expressing merlin in a novel human schwannoma model in nude mice. In culture, the introduction of an AAV1 vector encoding merlin into CRISPR-modified human NF2-null arachnoidal cells (ACs) or Schwann cells (SCs) was associated with decreased size and mTORC1 pathway activation consistent with restored merlin activity. In vivo, a single injection of AAV1-merlin directly into human NF2-null SC-derived tumors growing in the sciatic nerve of nude mice led to regression of tumors over a 10-week period, associated with a decrease in dividing cells and an increase in apoptosis, in comparison with vehicle. These studies establish that merlin re-expression via gene replacement in NF2-null schwannomas is sufficient to cause tumor regression, thereby potentially providing an effective treatment for NF2.

IMMU-14. COMPUTATIONAL DECONVOLUTION OF TUMOR-INFILTRATING IMMUNE COMPONENTS IN PEDIATRIC NERVOUS SYSTEM TUMORS

IntroductionIn the last decade, checkpoint inhibitor-based immunotherapy has been a groundbreaking development in the treatment of cancer. However, only a subset of patients treated with immune checkpoint inhibitors show long-lasting clinical benefit. Studies showed the tumor immune microenvironment (TME) as a particularly important factor influencing treatment response, critical for the design of other or combinatorial immunotherapy treatment strategies. Extensive research has been performed in the adult cancer field to unravel its immunogenomic aspects. However, in pediatric cancer this insight into tumor-infiltrating immune components is still lacking. This study aims to provide insight into the landscape of the immune microenvironment in pediatric primary nervous system tumors. MethodsBulk RNA-seq data of 936 pediatric primary solid tumors acquired from multiple international initiatives including Therapeutically Applicable Research To Generate Effective Treatments (TARGET), the International Cancer Genome Consortium (ICGC) and the Children’s Brain Tumor Tissue Consortium (CBTTC) were included in this study. We applied computational tumor immune microenvironment deconvolution, repurposed RNA-seq data to recover infiltrating T- and B-cell clonotypes and studied checkpoint gene expression across pediatric neural tumors. ResultsAmong pediatric neural tumors, embryonal tumors with multilayered rosettes (ETMR) and medulloblastomas (MB) were least immune infiltrated. Neuroblastomas (NBL) had the highest T-cell infiltration among pediatric cancers, while atypical teratoid/rhabdoid tumors (ATRT) had the highest levels of CD8 T cell infiltration among pediatric CNS tumors. While tumor mutational burden (TMB) was associated with immune cell infiltration in adult lung cancers and melanomas, we found no significant associations in pediatric cancers. The majority of NBL samples expressed LAG3, but ~10% of samples had elevated levels of TIM3 gene expression, suggesting a distinct mode of immunosuppression in this subset.

Twisted gastrulation signaling modulator 1 promotes the ability of glioma cell through activating Akt pathway.

Glioblastoma is one of the most common primary nervous system tumors and has a high mortality rate. It is necessary to explore a novel biological target and treatment approach. Twisted gastrulation signaling modulator 1 (TWSG1) is expressed in many tumors and closely related to tumor growth and proliferation. However, there is almost no report about the mechanism of TWSG1 in glioma. We used a glioma chip to detect the expression level of TWSG1 by Immunohistochemistry. The overexpression and silence experiments of TWSG1 were performed to assay the biological function of TWSG1 in LN229 and U251 cells. Subcutaneous xenograft mouse model presented the effect of TWSG1 expression on the malignant behavior of tumor cells. Experimental results displayed that the expression level for TWSG1 was substantially elevated in gliomas compared to that in normal brain tissue. The expression knockdown of TWSG1 caused inhibition of glioma cell proliferation. Besides, TWSG1 overexpression enhanced proliferation in glioma cells, and the capacity of proliferation was partly abolished by the PI3K inhibitor LY294002. We found that TWSG1 affected the activity of Akt signaling pathway. In conclusion, TWSG1 is overexpressed in glioma tissue and promotes tumor proliferation through Akt signaling pathway, may serve as a potential target for glioma diagnosis and therapy.

COVD-30. A SNAPSHOT OF THE IMPACT OF COVID-19 ON PATIENTS WITH NERVOUS SYSTEM TUMORS

BACKGROUNDThe impact of COVID-19 on patients with nervous system tumors is not known. This population is often immunosuppressed, susceptible to neurological complications, and requiring of frequent cancer care, all of which may confer vulnerability to poorer outcomes after infection.METHODSClinical data were obtained from structured electronic medical record elements, clinical note text and laboratory RESULTS: Each source was identified, integrated and analyzed using the Palantir Foundry platform (Syntropy), part of the Context Engine Data Management System through the MD Anderson Cancer Center (MDACC) IRB approved D3CODE initiative. The population of interest was patients diagnosed with COVID-19 who had been seen at the Brain and Spine Center for nervous system tumors.RESULTS8,177 ambulatory patients were seen at the Brain and Spine Center from 3/1/20–9/1/20. COVID status was known for 1,753 (21%). Sixty-one (0.7%) were COVID-19 positive. Of these, 17 had primary nervous system tumors. Seven (41%) were treated in the emergency department or hospital for infection. Two were symptomatic but did not require further care. Eight were asymptomatic. Nine (53%) had alterations in cancer management within one week of COVID-19 diagnosis – delayed surgery (3), delayed/interrupted chemotherapy (2), delayed/interrupted radiation (2), cancer treatment discontinued (2). Eight patients (47%) had no clear impact of infection on their cancer treatment, three were on surveillance. Three (18%) unique patients had neurological symptoms attributed to/exacerbated by COVID-19 – encephalopathy (2), seizure (2), stroke (1).CONCLUSIONNo deleterious effects of alterations in cancer management after COVID-19 infection have been identified thus far, though longitudinal follow up is warranted. Our results suggest that COVID-19 infection frequently incurs medical complications or alterations in cancer treatment. The potential impacts of COVID-19 on our vulnerable neuro-oncology patient population should be further explored, and attention to these potential implications for our patients is warranted by treating clinicians.

Prognostic values of preoperative albumin to globulin ratio for predicting clinical outcome in patients with high-grade gliomas

Background: Gliomas was the most common primary central nervous system tumors which have an increased morbidity in recent years. And the clinical prognosis of high-grade gliomas (HGG, WHO grade III to IV) was most with an average survival rate of only dozens of months. Many researchers concluded that the level of preoperative albumin-to-globulin ratio (AGR) could predict the clinical outcome of patients with solid malignant tumors. Methods: Two hundred and thirty-two cases of patients who were diagnosed HGG by pathology were enrolled in the study. The relevant data of the cohort included sex, age, preoperative Karnofsky performance score (KPS), extent of resection, albumin count and globulin count, isocitrate dehydrogenase (IDH) and survival time were collected. The survival rate was obtained by using the Kaplan-Meier method. The cut-off value of AGR was determined by X-tile software. Univariate survival analysis was performed by the log-rank method. Proportional hazards model (Cox model) was performed for multivariate analysis. Results: The optimal cut-off value of AGR was 1.32. Results showed that the preoperative AGR was correlated with clinical prognosis of patients with HGG, and the survival time of the patients with high AGR (AGR >1.32) was significantly longer. Moreover, the prognosis of patients with high AGR was better in IDH wild-type HGG. Conclusions: Preoperative AGR might predict the clinical prognosis of patients with HGG.

Rosette-forming glioneuronal tumor: an update.

Rosette-forming glioneuronal tumor (RGNT) is a rare and distinct primary nervous system tumor. The literature on this novel neoplasm is sparse and limited to mostly case reports. Reviews on the characteristics of this tumor are fewer and far between with the latest up to a decade old. We thus provide a comprehensive review of recent literature to characterize presenting symptoms, radiological evidence, treatment options, and prognosis of this novel neoplasm. A Medline search for case reports detailing primary rosette-forming glioneuronal tumors was performed. RGNTs are a benign tumor of indolent course with mixed glial and neurocytic components. There is a slight female predominance with mean age of presentation at 23.57years. Headaches, visual disturbances, and nausea and vomiting are the most common symptoms. Most RGNTs have solid and cystic components, arising most frequently in the fourth ventricle or cerebellum. Management is usually through surgery with gross total resection (GTR) providing better prognosis.

Temporal and Geographic Clustering of Polyomavirus-Associated Olfactory Tumors in 10 Free-Ranging Raccoons (Procyon lotor)

Reports of primary nervous system tumors in wild raccoons are extremely rare. Olfactory tumors were diagnosed postmortem in 9 free-ranging raccoons from 4 contiguous counties in California and 1 raccoon from Oregon within a 26-month period between 2010 and 2012. We describe the geographic and temporal features of these 10 cases, including the laboratory diagnostic investigations and the neuropathologic, immunohistochemical, and ultrastructural characteristics of these tumors in the affected animals. All 9 raccoons from California were found within a localized geographic region of the San Francisco Bay Area (within a 44.13-km radius). The tight temporal and geographic clustering and consistent anatomic location in the olfactory system of tumor types not previously described in raccoons (malignant peripheral nerve sheath tumors and undifferentiated sarcomas) strongly suggest either a common cause or a precipitating factor leading to induction or potentiation of neuro-oncogenesis and so prompted an extensive diagnostic investigation to explore possible oncogenic infectious and/or toxic causes. By a consensus polymerase chain reaction strategy, a novel, recently reported polyomavirus called raccoon polyomavirus was identified in all 10 tumors but not in the normal brain tissue from the affected animals, suggesting that the virus might play a role in neuro-oncogenesis. In addition, expression of the viral protein T antigen was detected in all tumors containing the viral sequences. We discuss the potential role of raccoon polyomavirus as an oncogenic virus.

Novel Oncogenic SMO and AKT1 Mutations in Meningiomas

Introduction: Meningiomas are the most common primary nervous system tumor. Although many of these are benign in histology and location, resection of skull base meningiomas can be associated with higher morbidity, and recurrence rates are not insignificant. Higher grade meningiomas recur with greater frequency and affect long-term survival as well. The tumor suppressor NF2 is disrupted in approximately half of meningiomas, but the complete spectrum of genetic changes remains undefined.

Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations

Meningiomas are the most common primary nervous system tumor. The tumor suppressor NF2 is disrupted in approximately half of meningiomas1 but the complete spectrum of genetic changes remains undefined. We performed whole-genome or whole-exome sequencing on 17 meningiomas and focused sequencing on an additional 48 tumors to identify and validate somatic genetic alterations. Most meningiomas exhibited simple genomes, with fewer mutations, rearrangements, and copy-number alterations than reported in other adult tumors. However, several meningiomas harbored more complex patterns of copy-number changes and rearrangements including one tumor with chromothripsis. We confirmed focal NF2 inactivation in 43% of tumors and found alterations in epigenetic modifiers among an additional 8% of tumors. A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (E17K) and SMO (W535L) and exhibited immunohistochemical evidence of activation of their pathways. These mutations were present in therapeutically challenging tumors of the skull base and higher grade. These results begin to define the spectrum of genetic alterations in meningiomas and identify potential therapeutic targets.

Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma

Missense mutations of the V600E type constitute the vast majority of tumor-associated somatic alterations in the v-RAF murine sarcoma viral oncogene homolog B1 (BRAF) gene. Initially described in melanoma, colon and papillary thyroid carcinoma, these alterations have also been observed in primary nervous system tumors albeit at a low frequency. We analyzed exon 15 of BRAF spanning the V600 locus by direct sequencing in 1,320 adult and pediatric tumors of the nervous system including various types of glial, embryonal, neuronal and glioneuronal, meningeal, adenohypophyseal/sellar, and peripheral nervous system tumors. A total of 96 BRAF mutations were detected; 93 of the V600E type and 3 cases with a three base pair insertion between codons 599 and 600. The highest frequencies of BRAF (V600E) mutations were found in WHO grade II pleomorphic xanthoastrocytomas (42/64; 66%) and pleomorphic xanthoastrocytomas with anaplasia (15/23; 65%), as well as WHO grade I gangliogliomas (14/77; 18%), WHO grade III anaplastic gangliogliomas (3/6) and pilocytic astrocytomas (9/97; 9%). In pilocytic astrocytomas BRAF (V600E) mutation was strongly associated with extra-cerebellar location (p=0.009) and was most frequent in diencephalic tumors (4/12; 33%). Glioblastomas and other gliomas were characterized by a low frequency or absence of mutations. No mutations were detected in non-glial tumors, including embryonal tumors, meningiomas, nerve sheath tumors and pituitary adenomas. The high mutation frequencies in pleomorphic xanthoastrocytomas, gangliogliomas and extra-cerebellar pilocytic astrocytomas implicate BRAF (V600E) mutation as a valuable diagnostic marker for these rare tumor entities. Future clinical trials should address whether BRAF (V600E) mutant brain tumor patients will benefit from BRAF (V600E)-directed targeted therapies.

Knockdown of STAT3 expression by RNAi suppresses growth and induces apoptosis and differentiation in glioblastoma stem cells

Glioblastoma is a highly lethal brain tumor of the human primary nervous system tumors. Previous studies demonstrated that glioblastoma stem cells were able to initiate and reform the original cancer. In this study, we found that there were expression and activation of STAT3, a key signal transduction factor and oncoprotein, in human glioblastoma stem cells (GSCs). STAT3 plays a key role in proliferation, apoptosis and differentiation in embryonic stem cells and several cancer types. To investigate the effects of STAT3 on human GSCs, the expression and activation of STAT3 were suppressed by RNAi mediated with lentivirus. We demonstrated that siRNA of STAT3 significantly suppressed STAT3 expression and activation and resulted in inhibition of cell growth in GSCs. Knockdown of STAT3 induces apoptosis and reduces significantly expression of Bcl-2 and cyclin-D in human primary GSCs, whereas no significance was achieved in BAX and caspase-3 expression. Inhibition of STAT3 expression is associated not only with decreasing of CD133+ cell proportion and increasing of GFAP and MBP expression, but also with decrease of the capacity to initiate a tumor in human primary GSCs. Together, these studies suggest that STAT3 is an important target for human GSCs in regulation of GSCs growth, apoptosis, differentiation and tumorigenic potential.

Primary pediatric central nervous system tumors statistic: study of 763 cases in a single institution

To investigate the epidemiology of primary pediatric central nervous system tumors. The clinical data of 763 pediatric patients aged under 18 diagnosed as with primary central nervous system tumors in the past 10 years in Huashan Hospital were analyzed retrospectively. The mean age was 12.68 and the male to female ratio was 1.56:1. Among the tumors intracranial tumors accounted for 93.4% (713/763), whereas spinal tumors accounted for 6.6% (50/763). 476 of the 763 tumors (62.4%) were supratentorial, including pineal-quadrigeminal tumors, which was predominant to infratentorial tumors (30.5%, 233/763). 688 of the 763 patients had pathological diagnosis. The most common 5 categories of tumors were: astrocytic tumors (25.7%, 177/688), craniopharyngioma (12.8%, 88/688), medulloblastoma (9.3%, 64/688), germ cell tumors (8.9%, 61/688), and pituitary adenoma (7.5%, 52/688). As the main neurological medical center in the southern part of China, the statistics of Huashan Hospital can be representative. The epidemiology of pediatric central nervous system tumors has its own specialty. Therefore, it is crucial to deal with primary pediatric central nervous system tumors according to children's characteristics.

Immunocytochemical detection of 14-3-3 in primary nervous system tumors

14-3-3 proteins have attracted much recent interest in the etiopathogenesis of human cancers owing to their involvement in the prevention of apoptosis. However, the expression of 14-3-3 in primary nervous system tumors has not been previously characterized. In this paper, Immunohistochemistry using a specific anti-14-3-3 antibody was performed on formalin-fixed, paraffin embedded archival tissue from 124 primary human nervous system tumors and 10 normal brain tissues. In the normal control brains, 14-3-3 immunoreactivity was localized mainly in the neuronal somata and processes, and some glial cells showed only weak immunoreactivity. However, 14-3-3 immunoreactivity was seen in the majority of astrocytomas [grade I (9/11), II (16/21), III (13/17), IV (17/21)]. There was no difference between the positive expression rates of 14-3-3 in different grades of astrocytomas (P = 0.968). But the intensity and degree of 14-3-3 immunoreactivity in diffuse astrocytomas, anaplastic astrocytoma, and glioblastoma multiformes showed trends with tumor grade, with glioblastomas having the highest positivity (P = 0.048). The 14-3-3 immunoreactivity was also seen in the majority of other gliomas [oligodendroglioma (2/3), anaplastic oligodendroglioma (4/4), ependymoma (1/2), anaplastic ependymoma (2/2), choroid plexus papilloma (3/3), pineocytoma (2/2), medulloblastoma (5/8)]. All meningiomas [syncytical (3), fibrous/fibroblastic (4), angiomatous (4), transitional/mixed (3)] were intensely and diffusely positive. All schwannomas (4), neurofibromas (2), pituitary adenomas (6) and craniopharyngiomas(4) also showed intense positive staining. These results showed that 14-3-3 is expressed in the majority of the primary human nervous system tumors. The up-regulated expression of 14-3-3 may be a common mechanism for evading apoptosis in most primary human nervous system tumors, and targeting 14-3-3 may be a novel promising strategy for the treatment of these tumors, especially for malignant tumors.

Radiotherapy for pediatric central nervous system tumors: a regional cancer centre experience.

The purpose of this review was to analyze outcomes for pediatric patients treated for more common (non-low grade glioma) primary central nervous system (CNS) tumors at a Regional (tertiary) Cancer Center. Comparison to reported results from other regional centres and results from the contemporary literature were made. The records of pediatric patients treated with radiotherapy at the London Regional Cancer Center (LRCC) for more common (non-low grade glioma) primary CNS tumors between 1980 and 2001 were reviewed. Details regarding tumor presentation, treatment and outcome were analyzed. Eighty-eight patients were eligible for the review. Twenty-nine patients with malignant glioma, 37 patients with medulloblastoma or primitive neuroectodermal tumor (PNET), 15 patients with brainstem glioma, 4 with ependymoma and 3 with germ cell tumors were treated during this time period. Average follow-up for the group was 5 years (range 4 months to 19 years). Five-year overall, progression free and cause specific survival were 45, 42 and 50%, respectively. For patients with malignant glioma median progression free and overall survival was 20 and 29 months. For patients with brainstem glioma median progression free and overall survival was 9 and 13 months. For medulloblastoma, 5-year progression free, and overall survival was 60 and 59%. RESULTS of this retrospective review of pediatric patients treated at a regional cancer center for primary CNS tumors (other than low grade glioma) were comparable to contemporary results reported by other Canadian centers and North American co-operative group trials.

Major vault protein/lung resistance-related protein (MVP/LRP) expression in nervous system tumors.

Lung resistance-related protein (LRP) was identified as the major vault protein (MVP), the main component of multimeric vault particles. It functions as a transport-associated protein that can be associated with multidrug resistance. In previous studies, expression of MVP/LRP has been documented in tumors of various types. In general, good correlations have been reported for expression of MVP/LRP and decreased sensitivity to chemotherapy and poor prognosis. MVP/LRP expression has been documented in glioblastomas, but its expression in nervous system tumors in general has not been well characterized. Immunohistochemistry using anti-human MVP/LRP antibody (LRP-56) was performed on formalin-fixed, paraffin-embedded archival tissue from 69 primary central nervous system tumors. Expression of MVP/LRP was observed in 81.2% (56/69) of primary nervous system tumors, including astrocytomas (11/13), oligodendrogliomas (1/2), oligoastrocytomas (5/5), ependymoma (1/1), meningiomas (35/45), schwannomas (2/2), and neurofibroma (1/1). Various degrees and distributions of immunoreactivity to MVP/ LRP were observed. Neither the presence nor the degree of immunoreactivity to MVP/LRP showed any correlation with either tumor grade or the presence of brain invasion.

Expression of survivin, an inhibitor of apoptosis protein, in tumors of the nervous system.

Survivin is an inhibitor of apoptosis protein that blocks apoptosis by binding to caspases-3 and -7. It is highly expressed in less-differentiated embryonic cells and rapidly dividing tumors, but not in terminally differentiated adult tissues. Elevated survivin levels are found in malignant systemic tumors, and are associated with chemo-resistance, radiation resistance, and poor prognosis. However, expression of survivin in primary nervous system tumors has not been previously characterized. Immunohistochemistry using anti-human survivin antibody (SURV11-A) was performed on formalin-fixed, paraffin-embedded archival tissue from 112 primary central nervous system tumors. Survivin immunoreactivity was seen in most diffuse astrocytomas [WHO II (2/4), III (3/3), IV (9/10), giant-cell glioblastoma (1), and gliosarcoma (1)]. The intensity and degree of survivin expression showed trends with tumor grade, with glioblastomas having the highest positivity. Pilocytic astrocytomas (5) and pleomorphic xanthoastrocytoma (1) were positive to a lesser degree. In oligodendrogliomas (6) and mixed oligo-astrocytomas [grade II (5), II-III (3), and III (7)], oligodendroglial elements appear to be negative compared to positive mini-gemistocytic oligodendrocytes. Ependymomas [grade II (6) and grade III (1)] were positive. Medulloblastomas (5) and retinoblastoma (1/4) showed focal positivity. All meningiomas [grade I (12), II (9), III (4), and grade I (3) and II (5) with frank brain invasion] were intensely positive. All schwannomas (11) and neurofibromas (6) were intensely positive. Thus, survivin is expressed in the majority of the primary nervous system tumors, particularly in glioblastomas, meningiomas, schwannomas and neurofibromas. Overexpression of survivin in meningiomas and benign peripheral nerve sheath tumors contrasts with previous reports relating it to rapid division and poor prognosis.

Hemangioblastomas del sistema nervioso en Camagüey (Cuba)

Hemangioblastomas of the central nervous system are the most frequent vascular tumours. They are 1 2% of primary nervous system tumours and 8 12% of the posterior fossa neoplasms. The objective is to analize clinical behaviour and long term results of sporadic and Von Hippel Lindau linked hemangioblastomas.It was searched the vacular Neurosurgical Data Bank at Manuel Ascunce Dom nech Hospital between January 1981 and January 2001 to select patients harvoring central nervous system hemangioblastomas histological confirmed. Melmo and Rosen criteria were utilized in Von Hippel Lindau syndrome. We performed a twenty years follow up of this patients.There were 12 patients with central nervous system hemangioblastomas. Average age of presentation was 41 years old. The first case had twenty years since the operation and the last, eight months. 83% were cystic and 17% were solids. There was not surgical mortality. One patient died of renal carcinoma 15 years after the operation on craneal fossa.Central nervous system hemangioblastomas are a cluster of challenge tumours. They are intraxial benign tumours with potential good outcome. We observed sporadic and Von Hippel Lindau linked hemangioblastomas. Patients with this syndrome need clinico imagenological screening to identify new associated lesions.