title: In situ detection of telomeres by fluorescence in situ hybridization and telomerase activity in glioblastoma multiforme: correlation with p53 status, EGFR, c-myc, MIB1, and Topoisomerase IIalpha protein expression.
abstract: Aberrations of genes/proteins regulating cell cycle and growth, increased proliferation and telomerase activity (TA) are documentable in glioblastoma multiforme. TA is more frequently detectable in secondary glioblastoma, which is also characterized by p53 mutation/overexpression. Discordant telomere (Te) length values have been reported in glioblastomas with and without TA. In 31 glioblastomas, in which pre-existing astrocytoma was not documented, we compared cases with and without TA for the expression of p53, EGFR, c-Myc, MIB-1 and Topoisomerase IIalpha; p53 mutations were also investigated by SSCP-PCR. Correlations were made with Te parameters [TePs: number (TeNo), length and area] as evaluated by image analysis in interphase nuclei of fluorescence in situ hybridization (FISH)-processed sections. We found no differences in the expression of the proteins evaluated and in TePs, except Te/nuclear area %, which was significantly lower in TA+ cases (p=0.02). TePs were, instead, inversely correlated with TA (p=0.0001). TA was positively correlated with MIB1 staining index in the TA+ cases (p=0.033), which also showed a positive correlation between TeNo and EGFR expression (p=0.042), and a trend towards a negative correlation between TeNo and p53 expression (p=0.05). Tumors overexpressing EGFR had a significantly shorter lifetime (p=0.0001). TeNo seems to be inversely correlated to tumor proliferation and lifetime in glioblastoma multiforme.
authors: Dipartimento di Patologia Umana e Oncologia, Sezione di Anatomia Patologica, Policlinico Le Scotte, I-53100 Siena, Italy. miracco@unisi.it
authors: Clelia
authors: C
authors: Miracco
authors: M Margherita
authors: MM
authors: De Santi
authors: Pietro
authors: P
authors: Luzi
authors: Anna Vittoria
authors: AV
authors: Lalinga
authors: Lorella
authors: L
authors: Laurini
authors: Maria Caterina
authors: MC
authors: De Nisi
authors: Giuseppina
authors: G
authors: Angeloni
authors: Marco
authors: M
authors: Brogi
authors: Concetta
authors: C
authors: Cardone
authors: Antonietta
authors: A
authors: Carducci
authors: Felice
authors: F
authors: Arcuri
authors: Piero
authors: P
authors: Tosi
authors: Giovanni
authors: G
authors: Rubino
authors: Luigi
authors: L
authors: Pirtoli
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000951:Antigens, Neoplasm; D001932:Brain Neoplasms / Q000201:enzymology; D002455:Cell Division; D002648:Child; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins; D066246:ErbB Receptors / Q000378:metabolism; D005909:Glioblastoma / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007527:Isoenzymes / Q000378:metabolism; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000378:metabolism; D008875:Middle Aged; D018807:Polymorphism, Single-Stranded Conformational; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000648:ultrastructure*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D019394:Ki-67 Antigen; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors; D019098:Telomerase; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D004250:DNA Topoisomerases, Type II