胶质细胞及胶质瘤细胞分泌β-微量蛋白

目的探索神经胶质细胞及人脑胶质瘤细胞是否能分泌β-tp。方法用ELlSA方法分析了胶质瘤病人脑脊液中和细胞培养液中β-tp水平。结果3种胶质细胞瘤和患者脑脊液中均能测得β-tp,其浓度是正常人的10～12倍。培养的大鼠胶质细胞随细胞数增加而β-tp水平增高。在胶质瘤细胞株(SHG-44,U-251,BT-325)培液中β-tp浓度与细胞增殖的增加成正比。但在非胶质瘤细胞株,如卵巢癌细胞,神经母细胞瘤细胞及前列腺癌细胞株等,β-tp的浓度与细胞增殖的趋势相反。结论胶质细胞和人脑胶质瘤细胞能分泌β-tp,细胞分泌β-tp水平的高低由细胞类型及细胞的多寡决定。     

婚姻状况对少突胶质细胞瘤患者预后的影响

目的:探讨少突胶质细胞瘤患者婚姻状况与预后之间的关系。方法:纳入SEER数据库中自1973-2015年诊断为少突胶质细胞瘤的4 282例患者。通过Kaplan-Meier法分析患者生存率,Cox回归模型分析影响生存的独立危险因素。结果:单因素分析显示,性别、年龄、手术情况、原发灶部位、婚姻状况与少突胶质细胞瘤患者生存期相关（P<0.01）。多因素分析发现,婚姻状况是患者生存的独立预后因素（P<0.05）,在相同性别、年龄范围、手术治疗情况下,丧偶仍是患者的独立危险因素（P<0.01）。结论:婚姻状况与少突胶质细胞瘤患者生存期密切相关,丧偶增加患者的死亡风险。     

Bcl-2 promotes malignant progression in a PDGF-B-dependent murine model of oligodendroglioma

A significant subset of gliomas arises after activation of the proproliferative platelet-derived growth factor (PDGF) pathway. The progression of low-grade gliomas to more malignant tumors may be due to oncogenic cellular programs combining with those suppressing apoptosis. Antiapoptotic genes are overexpressed in a variety of cancers, and the antiapoptotic gene, BCL2, is associated with treatment resistance and tumor recurrence in gliomas. However, the impact of antiapoptotic gene expression to tumor formation and progression is unclear. We overexpressed Bcl-2 in a PDGFB-dependent mouse model of oligodendroglioma, a common glioma subtype, to assess its effect in vivo. We hypothesized that the antiapoptotic effect would complement the proproliferative effect of PDGFB to promote tumor formation and progression to anaplastic oligodendroglioma (AO). Here, we show that coexpression of PDGFB and Bcl-2 results in a higher overall tumor formation rate compared to PDGFB alone. Coexpression of PDGFB and Bcl-2 promotes progression to AO with prominent foci of necrosis, a feature of high-grade gliomas. Median tumor latency was shorter in mice injected with PDGFB and Bcl-2 compared to those injected with PDGFB alone. Although independent expression of Bcl-2 was insufficient to induce tumors, suppression of apoptosis (detected by cleaved caspase-3 expression) was more pronounced in AOs induced by PDGFB and Bcl-2 compared to those induced by PDGFB alone. Tumor cell proliferation (detected by phosphohistone H3 activity) was also more robust in high-grade tumors induced by PDGFB and Bcl-2. Our results indicate that suppressed apoptosis enhances oligodendroglioma formation and engenders a more malignant phenotype.     

Alpha-internexin expression predicts outcome in anaplastic oligodendroglial tumors and may positively impact the efficacy of chemotherapy: European organization for research and treatment of cancer trial 26951

BACKGROUND:

Although it has been demonstrated that the neuronal intermediate filament alpha‐internexin (INA) is closely related to 1p19q codeletion in gliomas, its prognostic and predictive value has not yet been confirmed in a prospective trial. The authors of this report assessed the prognostic significance of INA expression and its correlation with relevant clinical and molecular characteristics in the prospective, randomized European Organization for Research and Treatment of Cancer (EORTC) 26951 trial of adjuvant procarbazine, lomustine, and vincristine (PCV) in patients with anaplastic oligodendroglial tumors (AOTs).

METHODS:

INA immunohistochemistry expression in tumors from 92 patients who were included in the EORTC 26951 trial was analyzed independently by 2 observers and was correlated with relevant clinical characteristics, including progression‐free survival (PFS) and overall survival (OS), and with molecular features, including 1p/19q codeletion, isocitrate dehydrogenase 1 and 2 gene (IDH1/IDH2) mutation, and O‐6 methylguanine‐DNA methyltransferase (MGMT) promoter methylation status.

RESULTS:

INA expression was observed in 33 tumors and was strongly correlated with 1p/19q codeletion, IDH1 mutations, and MGMT promoter methylation. It was associated with significantly better PFS and OS independent of the treatment received. By using Cox proportional hazard modeling for OS with stepwise selection, INA expression, patient age, and performance status were identified as independent prognostic factors. The results indicated that INA expression may have an impact on the efficacy of combined radiotherapy plus PCV.

CONCLUSIONS:

In a homogeneously treated group of patients with grade III AOTs, INA expression had strong favorable prognostic significance for OS and may have predictive value for sensitivity to chemotherapy. Cancer 2011. © 2011 American Cancer Society.     

Extracranial metastases of anaplastic oligodendroglioma

Extracranial metastasis of a malignant glioma is rare, possibly due to the lack of lymphatic drainage in the brain and because these tumors are unable to penetrate blood vessels. Extracranial metastasis of an anaplastic oligodendroglioma (ODG) is exceptionally rare. We present a 55-year-old male patient with diffuse extracranial metastases from a temporal anaplastic ODG, 11 months after cranial surgery. Anaplastic ODG, may spread to the other parts of the body. If patients with these tumors have neck or back pain, spinal metastasis should be included in the differential diagnosis and further investigated.     

The impact of molecular and clinical factors on patient outcome in oligodendroglioma from 20 years’ experience at a single centre

The increased chemosensitivity of oligodendroglial tumours has been associated with loss of heterozygosity (LOH) of the p arm of chromosome 1 and the q arm of chromosome 19 (LOH 1p/19q). Other clinical and molecular factors have also been identified as being prognostic and predictive of treatment outcome. We reviewed 105 patients with oligodendroglioma treated at a single centre over 20 years. Median survival in oligodendroglioma patients with LOH 1p/19q was significantly longer (10.9 vs. 2.0 years). In the anaplastic oligodendroglioma group, univariate analysis demonstrated decreased patient age, presentation with seizures, use of adjuvant chemotherapy and LOH 1p/19q as predictors of improved survival. Multivariate analysis confirmed LOH 1p/19q as a significant predictor of improved survival (hazard ratio, 3.4; p = 0.015). Median survival in patients with anaplastic oligodendroglioma with LOH 1p/19q was 15.4 years vs. 1.2 years for those without LOH 1p/19q. This study confirms the utility of LOH 1p/19q as a prognostic marker in oligodendroglioma.     

Segregation of non‐p.R132H mutations in IDH1 in distinct molecular subtypes of glioma

Mutations in the gene encoding the isocitrate dehydrogenase 1 gene (IDH1) occur at a high frequency (up to 80%) in many different subtypes of glioma. In this study, we have screened for IDH1 mutations in a cohort of 496 gliomas. IDH1 mutations were most frequently observed in low grade gliomas with c.395G>A (p.R132H) representing >90% of all IDH1 mutations. Interestingly, non‐p.R132H mutations segregate in distinct histological and molecular subtypes of glioma. Histologically, they occur sporadically in classic oligodendrogliomas and at significantly higher frequency in other grade II and III gliomas. Genetically, non‐p.R132H mutations occur in tumors with TP53 mutation, are virtually absent in tumors with loss of heterozygosity on 1p and 19q and accumulate in distinct (gene‐expression profiling based) intrinsic molecular subtypes. The IDH1 mutation type does not affect patient survival. Our results were validated on an independent sample cohort, indicating that the IDH1 mutation spectrum may aid glioma subtype classification. Functional differences between p.R132H and non‐p.R132H mutated IDH1 may explain the segregation in distinct glioma subtypes. © 2010 Wiley‐Liss, Inc.     

Intraoperative imprint cytology of central neurocytoma: The great oligodendroglioma mimicker

Intraoperative cytologic evaluation of brain tumors has been used either to render a preliminary interpretation or more often as a complement to frozen section examination. Central neurocytoma is a intraventricular neoplasm, typically located in the region of the foramen of Monro, affecting mostly young to middle age adults. Histologically, central neurocytomas are characterized by monotonous cells with round nuclei and neuronal differentiation within a rich capillary network. Their distinction during intraoperative consultations from oligodendroglioma, ependymoma (mainly clear cell ependymoma), and non‐Hodgkin lymphoma can be a diagnostic challenge. We report a case of a 19‐year‐old female with an intraventricular tumor where imprint cytology preparations were crucial for the intraoperative diagnosis of central neurocytoma. Imprint cytology preparations show a round cell neoplasm associated with neuropil clumps and short straight capillaries admixed with tumor cell clusters. To the best of our knowledge, only a few cases describing the cytologic findings of central neurocytomas have been reported in the medical literature. The differential diagnosis, tissue correlation, clinical‐radiologic features, and ancillary studies are discussed. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.