title: Immunohistochemical expression of cyclin D1 is higher in supratentorial ependymomas and predicts relapses in gross total resection cases.
abstract: Ependymomas are tumors of the CNS. Although cyclin D1 overexpression has been related to several cancers, its prognostic value in ependymomas has not yet been fully established. We evaluated cyclin D1 expression by an immunohistochemistry analysis of 149 samples of ependymomas, including some relapses, corresponding to 121 patients. Eighty-one patients were adults, 60 were intracranial cases and 92 tumors were grade II. Gross total resection (GTR) was achieved in 62% of cases, and relapse was confirmed in 41.4% of cases. Cyclin D1 protein expression was analyzed by immunohistochemistry and scored with a labeling index (LI) calculated as the percentage of positively stained cells by intensity. We also analyzed expression of CCND1 and NOTCH1 in 33 samples of ependymoma by quantitative real-time PCR. A correlation between cyclin D1 LI score and anaplastic cases (P < 0.001), supratentorial location (P < 0.001) and age (P = 0.001) were observed. A stratified analysis demonstrated that cyclin D1 protein expression was strong in tumors with a supratentorial location, independent of the histological grade or age. Relapse was more frequent in cases with a higher cyclin D1 LI score (P = 0.046), and correlation with progression-free survival was observed in cases with GTR (P = 0.002). Only spinal canal tumor location and GTR were suggestive markers of PFS in multivarite analyses. Higher expression levels were observed in anaplastic cases for CCND1 (P = 0.002), in supratentorial cases for CCND1 (P = 0.008) and NOTCH1 (P = 0.011). There were correlations between the cyclin D1 mRNA and protein expression levels (P < 0.0001) and between CCND1 and NOTCH1 expression levels (P = 0.003). Higher cyclin D1 LI was predominant in supratentorial location and predict relapse in GTR cases. Cyclin D1 could be used as an immunohistochemical marker to guide follow-up and treatment in these cases.
authors.affiliation: Laboratory of Cellular and Molecular Biology, Department of Neurology, University of Sao Paulo, Sao Paulo, Brazil.|Division of Neurosurgery, Department of Neurology, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Fernanda Gonçalves
authors.identifier: http://orcid.org/0000-0003-3414-796X
authors.initials: FG
authors.lastname: de Andrade
authors.affiliation: Laboratory of Cellular and Molecular Biology, Department of Neurology, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Suely Kazue Nagahashi
authors.initials: SK
authors.lastname: Marie
authors.affiliation: Laboratory of Cellular and Molecular Biology, Department of Neurology, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Uno
authors.affiliation: Division of Neurosurgery, Department of Neurology, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Hamilton
authors.initials: H
authors.lastname: Matushita
authors.affiliation: Division of Neurosurgery, Department of Neurology, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Mario Augusto
authors.initials: MA
authors.lastname: Taricco
authors.affiliation: Division of Neurosurgery, Department of Neurology, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Manoel Jacobsen
authors.initials: MJ
authors.lastname: Teixeira
authors.affiliation: Pathology, Hospital das Clinicas, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Sergio
authors.initials: S
authors.lastname: Rosemberg
authors.affiliation: Laboratory of Cellular and Molecular Biology, Department of Neurology, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Sueli Mieko
authors.initials: SM
authors.lastname: Oba-Shinjo
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism*; D018572:Disease-Free Survival; D004806:Ependymoma / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D051881:Receptor, Notch1 / Q000378:metabolism; D015173:Supratentorial Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D019938:Cyclin D1
keywords: NOTCH1; cyclin D1; ependymoma; glioma; immunohistochemical markers