Epithelioid glioblastoma (eGBM) and pleomorphic xanthoastrocytoma (PXA) with anaplastically transformed foci (ePXA) show overlapping features. Eleven eGBMs and 5 ePXAs were reviewed and studied immunohistochemically. Fluorescence in situ hybridization for EGFR amplification, PTEN deletion and ODZ3 deletion was also performed, with Ilumina 450 methylome analysis obtained in five cases. The average age for eGBM was 30.9 (range 2-79) years, including five pediatric cases and a M : F ratio of 4.5. The ePXA patients had a M : F ratio of 4 and averaged 21.2 (range 10-38) years in age, including two pediatric cases. Six eGBMs and two ePXAs recurred (median recurrence interval of 12 and 3.3 months, respectively). All tumors were composed of solid sheets of loosely cohesive, "melanoma-like" cells with only limited infiltration. ePXAs showed lower grade foci with classic features of PXA. Both tumor types showed focal expression of epithelial and glial markers, retained INI1 and BRG1 expression, occasional CD34 positivity, and lack of mutant IDH1 (R132H) immunoreactivity. BRAF V600E mutation was present in four eGBMs and four ePXAs. ODZ3 deletion was detected in seven eGBMs and two ePXAs. EGFR amplification was absent. Methylome analysis showed that one ePXA and one eGBM clustered with PXAs, one eGBM clustered with low-grade gliomas, and two eGBMs clustered with pediatric-type glioblastomas. Common histologic, immunohistochemical, molecular and clinical features found in eGBM and ePXA suggest that they are closely related or the same entity. If the latter is true, the nomenclature and WHO grading remains to be resolved.

Human metapneumovirus (HMPV) is a recently discovered pathogen that causes a significant proportion of respiratory infections in young infants, the elderly and immunocompromised patients. Very little is known regarding the cellular signalling elicited by this virus in airway epithelial cells, the target of HMPV infection. In this study, we investigated the role of the RNA helicases retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-associated gene-5 (MDA-5) as the main pattern recognition receptors (PRRs) involved in viral detection and subsequent expression of proinflammatory and antiviral genes. HMPV infection readily induced RIG-I and MDA-5 gene and protein expression in A549 cells, a type II-like alveolar epithelial cell line. Expression of dominant-negative (DN) RIG-I or downregulation of RIG-I gene expression using small interfering RNA (siRNA) significantly decreased HMPV-induced beta interferon (IFN-b), interleukin (IL)-8 and RANTES gene transcription, by inhibiting viral-induced activation of nuclear factor (NF)-kB and interferon regulatory factor (IRF), leading to enhanced viral replication. On the other hand, MDA-5 did not seem to play a significant role in HMPV-induced cellular responses. Mitochondrial antiviral signalling protein (MAVS), an adaptor protein linking both RIG-I and MDA-5 to downstream activation of IRF-3 and NF-kB, was also necessary for HMPVinduced cellular signalling. Expression of a DN MAVS significantly reduced IFN-b and chemokine gene transcription, by inhibiting NF-kB-and IRF-dependent gene transcription, in response to HMPV infection. Our results show that HMPV activates the RIG-I-MAVS signalling pathway in airway epithelial cells, leading to the expression of important proinflammatory and antiviral molecules involved in the innate immune response to viruses. INTRODUCTIONHuman metapneumovirus (HMPV) is a recently identified respiratory RNA virus belonging to the family Paramyxoviridae. HMPV is responsible for a significant proportion of upper and lower respiratory tract infections in young children, the elderly and immunocompromised patients, causing bronchiolitis, croup, asthma exacerbation and even pneumonia (Boivin et al., 2002;Esper et al., 2003;Williams et al., 2004), second only to respiratory syncytial virus (RSV) (Kahn, 2006;Principi et al., 2006;Williams et al., 2004), also a paramyxovirus. While there is emerging literature on the clinical and epidemiological features of HMPV infection, very little is known regarding the cellular signalling activated by this pathogen in infected cells. We have recently demonstrated that HMPV is a potent stimulus for cytokine, chemokine and type I interferon (IFN) production in cultured human alveolar epithelial cells, and that HMPV-induced chemokine expression is dependent on viral replication (Bao et al., 2007). We have also shown that HMPV infection induces activation of nuclear factor (NF)-kB and interferon regulatory factor (IRF) transcription factors (Bao et al., 2007), which have been shown to play a fundamental ...

Serotype 19A was strongly associated with BPF. Vaccines containing this serotype will be important for prevention.