Oligoastrocytoma: A Vanishing Tumor Entity

Oligoastrocytoma (OA) was a glioma recognized in the current World Health Organization (WHO) classification of the central nervous system (CNS) tumors as a mixed tumor with an astrocytic and an oligodendroglial component. Its definability was, however, poor so that its prevalence varies in the various collections. A series of contributions of the literature and the “International Society of Neuropathology (ISN) – Haarlem Consensus” recently denied its existence as a tumor entity on the basis of 1p/19q, isocitrate dehydrogenase (IDH) and α-thalassemia/mental retardation syndrome X-linked (ATRX) status. Most tumors previously diagnosed as OAs were, therefore, reclassified as either oligodendrogliomas or astrocytomas

EMP3 (epithelial membrane protein 3)

Epithelial membrane protein 3 (EMP3) has recently been proposed as a candidate tumor suppressor gene (TSG) for some kinds of solid tumors. EMP3 down-regulation has been explained by its epigenetic silencing through aberrant hypermethylation of the promoter region. EMP3 repression in cancer seems to be an organ-specific phenomenon, common in neuroblastoma and gliomas, relatively common in breast cancer, and rare in esophageal squamous cell carcinoma (ESCC). Among cancer-derived cell lines, it prevails in neuroblastoma, breast cancer and ESCC whereas it is rare in glioma, non-small cell lung carcnoma (NSCLC), gastric and colon cancer-derived cell lines. EMP3 expression level is associated with clinical prognosis in neuoblastoma, ESCC, NSCLC and upper urinary tract urothelial carcinoma. In contrast, EMP3 expression may be a novel marker of tumor aggressiveness in breast cancer whereas in gliomas, EMP3 represssion by aberrant hypermethylation has a prognostic signifcance. In both tumor types, however, alternative mechanisms to the EMP3 epigenetic silencing may exist to explain EMP3 down-regulation. Moreover, EMP3 may be involved in the prostate cancer suscpetibility

Stat3 Expression and Its Correlation with Proliferation and Apoptosis/Autophagy in Gliomas

Signal transducer and activator of transcription-3 (Stat3) was studied along with several steps of the PI3/Akt pathway in a series of 64 gliomas that included both malignant and low-grade tumors, using quantitative immunohistochemistry, Western blotting, and molecular biology techniques. The goal of the study was to investigate whether activated Stat3 (phospho-Stat3) levels correlated with cell proliferation, apoptosis, and autophagy. Stat3 and activated Akt (phospho-Akt) expression increased with malignancy grade, but did not correlate with proliferation and survival within the category of glioblastomas. A correlation of Stat3 with Akt was found, indicating a regulation of the former by the PI3/Akt pathway, which, in turn, was in relation with EGFR amplification. Stat3 and Akt did not show any correlation with apoptosis, whereas they showed an inverse correlation with Beclin 1, a stimulator of autophagy, which was rarely positive in glioblastomas. Autophagy seems then to be inactivated in malignant gliomas

Antigenic and Genotypic Similarity between Primary Glioblastomas and Their Derived Neurospheres

Formation of neurospheres (NS) in cultures of glioblastomas (GBMs), with self-renewal, clonogenic capacities, and tumorigenicity following transplantation into immunodeficient mice, may denounce the existence of brain tumor stem cells (BTSCs) in vivo. In sixteen cell lines from resected primary glioblastomas, NS showed the same genetic alterations as primary tumors and the expression of stemness antigens. Adherent cells (AC), after adding 10% of fetal bovine serum (FBS) to the culture, were genetically different from NS and prevailingly expressed differentiation antigens. NS developed from a highly malignant tumor phenotype with proliferation, circumscribed necrosis, and high vessel density. Beside originating from transformed neural stem cells (NSCs), BTSCs may be contained within or correspond to dedifferentiated cells after mutation accumulation, which reacquire the expression of stemness antigens