title: p-CREB expression in human gliomas: potential use in the differential diagnosis between astrocytoma and oligodendroglioma.
abstract: Phosphorylated cyclic-AMP responsive element binding protein (p-CREB) is a transcription factor that is involved in gliomagenesis. For this reason, it was recently proposed as a potential therapeutic target in gliomas; however, gliomas comprise tumors with different biomolecular profile, clinical behavior, and response to chemotherapy. In the present study, we aimed to investigate whether p-CREB expression varies in the 2 main types of gliomas, astrocytomas and oligodendrogliomas. Thus, we analyzed the expression of p-CREB in a series of astrocytomas and oligodendrogliomas of different histologic grades by immunohistochemistry and Western blot analysis. p53 overexpression and the Ki-67 labeling index were also assessed in all the tumors. p-CREB immunohistochemical expression was present in 100% of the astrocytic tumors, but in only 46% of oligodendrogliomas (P = .0033 for grade II; P = .0041 for grade III tumors). Absence of p-CREB immunohistochemical expression was significantly associated with 1p/19q codeletion (P < .0001) and identified 1p/19q codeleted tumors, with 70% sensitivity and 100% specificity (area under the curve = 0.85; P < .0001). In addition, p-CREB expression correlated with higher Ki-67 labeling index (P = .049) and p53 overexpression (P < .0001) as well as with the histologic grade of astrocytomas (P = .044). Immunohistochemical results were further confirmed by Western blot analysis. Our findings demonstrate that astrocytomas and oligodendrogliomas are characterized by distinctive patterns of p-CREB expression. These distinct expression patterns might provide insight into the mechanism of tumorigenesis of glial tumors and represent a useful tool for the differential diagnosis of astrocytoma and oligodendroglioma.
authors.affiliation: Department of Human Pathology "Gaetano Barresi," AOU G. Martino, Pad D, Via Consolare Valeria, 98125 Messina, Italy. Electronic address: vbarresi@unime.it.
authors.forename: Valeria
authors.initials: V
authors.lastname: Barresi
authors.affiliation: Department of Neurosciences, AOU G. Martino, Pad D, Via Consolare Valeria, 98125 Messina, Italy. Electronic address: smondello@unime.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Mondello
authors.affiliation: Department of Human Pathology "Gaetano Barresi," AOU G. Martino, Pad D, Via Consolare Valeria, 98125 Messina, Italy. Electronic address: Gianni_branca@alice.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Branca
authors.affiliation: Department of Neurosciences, AOU G. Martino, Pad D, Via Consolare Valeria, 98125 Messina, Italy.
authors.forename: Thangavelu Soundara
authors.initials: TS
authors.lastname: Rajan
authors.affiliation: Department of Human Pathology "Gaetano Barresi," AOU G. Martino, Pad D, Via Consolare Valeria, 98125 Messina, Italy. Electronic address: evitarelli@unime.it.
authors.forename: Enrica
authors.initials: E
authors.lastname: Vitarelli
authors.affiliation: Department of Human Pathology "Gaetano Barresi," AOU G. Martino, Pad D, Via Consolare Valeria, 98125 Messina, Italy. Electronic address: tuccari@unime.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tuccari
mesh_terms: D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000175:diagnosis / Q000378:metabolism*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D002872:Chromosome Deletion; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D003937:Diagnosis, Differential; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008875:Middle Aged; D009837:Oligodendroglioma / Q000175:diagnosis / Q000378:metabolism*; D010766:Phosphorylation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D055815:Young Adult
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D016159:Tumor Suppressor Protein p53
keywords: 1p/19q codeletion; Astrocytoma; Oligodendroglioma; p-CREB; p53