Alpha Internexin: A Surrogate Marker for 1p/19q Codeletion and Prognostic Marker in Anaplastic (WHO grade III) Gliomas.

Background: The WHO 2016 classification of diffuse gliomas has incorporated molecular markers isocitrate dehydrogenase (IDH) gene mutations (IDHmut) and codeletion of chromosomal arms 1p and 19q (1p/19q codeletion) as tumor defining entities. The diagnosis of diffuse oligodendrogliomas (ODG) and anaplastic oligodendroglioma (AO) mandatorily requires the demonstration of IDH1 and/or IDH2 mutations along with 1p/19q codeletion, whereas the 1p/19q noncodeleted diffuse gliomas are labeled as astrocytomas. The current methodologies for assessing 1p/19q codeletion status are expensive and not widely available.

Proteomic profiling of medulloblastoma reveals novel proteins differentially expressed within each molecular subgroup.

Objectives: The objective of the study was to identify novel medulloblastoma (MB) biomarkers through proteomic profiling, correlate it with the molecular subgroups of MB and assess the clinical significance.

Methods: Archived paraffin embedded tumor tissue blocks from 118 MB patients, operated at our institute were retrieved. Clinical information was documented from the hospital database.

Granulomatous and lymphocytic hypophysitis - are they immunologically distinct?

Hypophysitis includes three histopathologically distinct entities - granulomatous, lymphocytic and xanthomatous forms. Etiopathogenesis and the immunological differences among these is not well characterized. This study aims to explore the immunopathogenesis of granulomatous and lymphocytic forms of hypophysitis.

Integrative functional genomic analysis identifies epigenetically regulated fibromodulin as an essential gene for glioma cell migration.

An integrative functional genomics study of multiple forms of data are vital for discovering molecular drivers of cancer development and progression. Here, we present an integrated genomic strategy utilizing DNA methylation and transcriptome profile data to discover epigenetically regulated genes implicated in cancer development and invasive progression. More specifically, this analysis identified fibromodulin (FMOD) as a glioblastoma (GBM) upregulated gene because of the loss of promoter methylation.

Insulin-like growth factor binding protein-2 regulates β-catenin signaling pathway in glioma cells and contributes to poor patient prognosis.

Background: Upregulation of insulin-like growth factor binding protein 2 (IGFBP-2) is often associated with aggressiveness of glioblastoma (GBM) and contributes to poor prognosis for GBM patients. In view of the regulation of β-catenin by IGFBP-2 in breast cancer and the crucial role of β-catenin pathway in glioma invasion, proliferation and maintenance of glioma stem cells, the mechanism of regulation of β-catenin by IGFBP-2, and its role in GBM prognosis was studied.

Methods: Regulation of the β-catenin pathway was studied by immunocytochemistry, Western blot analysis, luciferase assays, and real-time RT-PCR.

Prognostic significance of histomolecular subgroups of adult anaplastic (WHO Grade III) gliomas: applying the 'integrated' diagnosis approach.

Aims: Anaplastic gliomas (AGs; WHO Grade III) include anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) and are known to have variable prognosis. Since biomarkers have a major impact on prognosis of gliomas, we compared the prognostic significance of the established biomarkers of AGs and the 'histomolecular' subgroups based on the proposed International Society of Neuropathology-Haarlem ('ISN-Haarlem') guidelines, with the current WHO 2007 classification.

Methods: The study was carried out on formalin-fixed paraffin-embedded (FFPE) tissues from 91 adult patients with AG.

Manganese superoxide dismutase (MnSOD) is a malignant astrocytoma specific biomarker and associated with adverse prognosis in p53 expressing glioblastoma.

Background: Manganese super oxide dismutase (MnSOD) has been previously identified as one of the top regulated genes associated with poor survival in glioblastoma (GBM) patients. In the current study we have evaluated the protein expression of MnSOD across various grades of astrocytoma, studied its influence on survival of GBM patients and following recurrence.

Methods: The protein expression of MnSOD was analyzed on tumor tissue sections by immunohistochemistry on 30 diffuse astrocytomas (DA), 50 anaplastic astrocytomas (AA), 30 paired (primary and recurrent) GBM samples and 30 non-tumor brain tissues.

Glioblastoma-derived Macrophage Colony-stimulating Factor (MCSF) Induces Microglial Release of Insulin-like Growth Factor-binding Protein 1 (IGFBP1) to Promote Angiogenesis.

Glioblastoma (grade IV glioma/GBM) is the most common primary adult malignant brain tumor with poor prognosis. To characterize molecular determinants of tumor-stroma interaction in GBM, we profiled 48 serum cytokines and identified macrophage colony-stimulating factor (MCSF) as one of the elevated cytokines in sera from GBM patients. Both MCSF transcript and protein were up-regulated in GBM tissue samples through a spleen tyrosine kinase (SYK)-dependent activation of the PI3K-NFκB pathway.

Definition of a serum marker panel for glioblastoma discrimination and identification of Interleukin 1β in the microglial secretome as a novel mediator of endothelial cell survival induced by C-reactive protein.

Glioblastoma (GBM) is the most common malignant adult primary brain tumor. We profiled 724 cancer-associated proteins in sera of healthy individuals (n=27) and GBM (n=28) using antibody microarray. While 69 proteins exhibited differential abundance in GBM sera, a three-marker panel (LYAM1, BHE40 and CRP) could discriminate GBM sera from that of healthy donors with an accuracy of 89.

Methylation silencing of ULK2, an autophagy gene, is essential for astrocyte transformation and tumor growth.

Glioblastoma (GBM) is the most aggressive type of brain tumor and shows very poor prognosis. Here, using genome-wide methylation analysis, we show that G-CIMP+ and G-CIMP-subtypes enrich distinct classes of biological processes. One of the hypermethylated genes in GBM, ULK2, an upstream autophagy inducer, was found to be down-regulated in GBM.

Implications of MGMT methylation status in pituitary adenoma.

Background: Very little literature exists on frequency of MGMT methylation status in pituitary adenoma. We assessed the frequency of MGMT methylation and protein expression in pituitary adenoma and correlated with patients' age group and prognosis.

Methods: Tumor tissues from 30 patients with pituitary adenoma were evaluated for MGMT promoter methylation status by methylation specific PCR method.

IDH1 mutations in diffusely infiltrating astrocytomas: grade specificity, association with protein expression, and clinical relevance.

IDH1 mutations are frequent genetic alterations in low-grade diffuse gliomas and secondary glioblastoma (GBM). To validate mutation frequency, IDH1 gene at codon 132 was sequenced in 74 diffusely infiltrating astrocytomas: diffuse astrocytoma (DA; World Health Organization [WHO] grade II), anaplastic astrocytoma (AA; WHO grade III), and GBM (WHO grade IV). All cases were immunostained with IDH1-R132H monoclonal antibody.