Glial differentiation predicts poor clinical outcome in primitive neuroectodermal brain tumors

Abstract

Primitive neuroectodermal tumors (PNETs) of the central nervous system, including medulloblastomas (PNET/MB), are the most common malignant brain tumor of childhood. These tumors often express proteins characteristic of glial differentiation (glial fibrillary acidic protein, GFAP), neuronal differentiation (neurofilament proteins, NFPs), and/or photoreceptor differentiation (retinal-S antigen). To identify biological factors of prognostic significance in PNETs, the expression of glial, neuronal, or photoreceptor antigens was evaluated in the tumor specimens of 86 patients with PNETs by immunohistochemistry after microwave antigen enhancement. Patterns of differentiation were then compared with patient relapse-free survival. Multivariate analysis of PNET immunohistochemistry and clinical variables indicated GFAP expression conferred a 6.7-fold greater risk of relapse than tumors that did not express GFAP or NFPs. Increased risk of relapse was directly related to the amount of GFAP expression. Tumors exhibiting clumps or sheets of GFAP-staining cells were associated with a 3.0-fold increased risk of relapse compared with tumors that did not express GFAP, irrespective of immunohistochemical evidence of other differentiation, while scattered GFAP staining was not associated with increased risk of relapse. These findings indicate that expression of GFAP in PNETs has prognostic power comparable with the most significant clinical factors currently used to predict clinical outcome.

Papillary Glioneuronal Tumour in a 4-Year-Old

“…The mean age of the group was 27.2 ± 12.7 years, though this further case would suggest that the diagnosis merits consideration outside these age limits. Of note, statistically by mean age this tumour was more likely to be a primitive neuroectodermal tumour (6.7 years) [3]or neuroblastoma (9.3 years) [4]. …”

Prevention of experimental allergic encephalomyelitis by targeting nitric oxide and peroxynitrite: Implications for the treatment of multiple sclerosis

“…To define cell types positive for iNOS mRNA expression in frozen brain sections, immunohistochemistry was performed in conjunction with RT-IS-PCR as described (7,14). Staining was carried out with a variety of antibodies and lectins: (i) cells of the macrophage͞microglia cell lineage were identified with rhodamine-conjugated Ricinus communis agglutinin (RCA-1) lectin (Sigma), which specifically binds these cells (15); (ii) microvascular endothelial cells were distinguished with polyclonal antibodies specific for von Willebrand factor (vWF; factor VIII-related antigen), which is expressed in the cytoplasm of human endothelial cells (Sigma) (16); (iii) astrocytes were identified using polyclonal antibodies against glial fibrillary acidic protein (GFAP) (17); (iv) oligodendrocytes were stained with monoclonal antibodies to 2Ј,3Ј-cyclic nucleotide-3Ј-phosphodiesterase (CNPase; Sigma), which is specifically expressed in oligodendrocytes and Schwann cells (18); and (v) neurons were identified with a cocktail of three monoclonal antibodies (NF5139, NF160, and NF389), which bind three different neurofilament epitopes (19). Antibodies to nitrotyrosine were purchased from Upstate Biotechnology (Lake Placid, NY).…”

“…This immunization protocol results in a progressive, often fatal, form of acute EAE in female SWXJ-14 mice (21,22). Clinical symptoms in these mice manifest first as an ascending paralysis approximately 13 days after immunization, with rapid disease progression until death at days [16][17][18][19][20]. The clinical signs of EAE were scored as: (i) piloerection, tail weakness; (ii) tail paralysis; (iii) tail paralysis plus hind limb weakness͞paralysis; (iv) tail, hind and fore limb paralysis; (v) moribund.…”

Expression of the Neurotrophin Receptor p75NTRin Medulloblastomas Is Correlated with Distinct Histological and Clinical Features: Evidence for a Medulloblastoma Subtype Derived from the External Granule Cell Layer

“…Glial differentiation in PNET/MB, defined by the expression of GFAP, has been the subject of many studies (2,3,(7)(8)(9). Herpers and Budka (46) found expression of GFAP exclusively in DMBs.…”