title: Expression of phosphoprotein enriched in astrocytes 15 kDa (PEA-15) in astrocytic tumors: a novel approach of correlating malignancy grade and prognosis.
abstract: Phosphoprotein enriched in astrocytes 15 kDa (PEA-15) is a multifunctional protein that was first identified in brain astrocytes and that has subsequently been shown to be expressed in different tissues. Despite its many important roles, the clinical significance of PEA-15 expression levels in astrocytic tumors has yet to be properly defined. We studied the PEA-15 expression pattern of 65 patients [diagnosed according to World Health Organization (WHO) criteria] with diffuse astrocytoma (WHO grade II), anaplastic astrocytoma (grade III), and glioblastoma (grade IV). PEA-15 expression levels were immunohistochemically measured and categorized as no, low, or high expression. All tumors expressed PEA-15 in our study. Twenty-three (35.4%) and 42 (64.6%) tumors expressed low and high PEA-15 levels, respectively. In grade II astrocytoma (diffuse astrocytoma) and grade III astrocytoma (anaplastic astrocytoma), 100% and 88.9% of patients expressed high PEA-15 levels, respectively, while a smaller number (50%) of patients with grade IV astrocytoma (glioblastoma) expressed high PEA-15 levels. PEA-15 expression level was inversely associated with WHO grade (P = 0.0006). Next, we evaluated prognosis and PEA-15 expression levels in 43 patients with high-grade astrocytomas based on the following parameters: age, gender, WHO grade, surgical resection extent, MIB-1 labeling index (LI), and PEA-15 expression level. Multivariable analyses revealed that high PEA-15 expression level displayed a significant correlation with longer overall survival (OS) in high-grade astrocytomas (P = 0.0024). Patients with total resection survived significantly longer (P = 0.0044) than those with lower resection extent, while patients with MIB-1 labeling index ≤25% indicated significant (P = 0.0434) correlation with OS as well. In conclusion, PEA-15 expression level was inversely associated with WHO grade and may serve as an important prognostic factor for high-grade astrocytomas.
authors.affiliation: Department of Neurosurgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Yamasaki
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kajiwara
authors.forename: Taiichi
authors.initials: T
authors.lastname: Saito
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishimoto
authors.forename: Chandra
authors.initials: C
authors.lastname: Bartholomeusz
authors.forename: Naoto T
authors.initials: NT
authors.lastname: Ueno
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kurisu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins; D001254:Astrocytoma / Q000145:classification / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D001932:Brain Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; C092039:PEA15 protein, human; D010750:Phosphoproteins
references.citation: J Neurosci. 1999 Oct 1;19(19):8244-51
references.pmid: 10493725
references.citation: Cancer Res. 2007 Feb 15;67(4):1536-44
references.pmid: 17308092
references.citation: Mol Biol Cell. 2005 Aug;16(8):3552-61
references.pmid: 15917297
references.citation: Cancer. 1988 Nov 15;62(10):2152-65
references.pmid: 3179928
references.citation: Neuropathology. 2008 Oct;28(5):507-15
references.pmid: 18410277
references.citation: Lancet Oncol. 2005 May;6(5):322-7
references.pmid: 15863380
references.citation: Mol Biol Cell. 2006 Dec;17(12):5141-52
references.pmid: 16987961
references.citation: Oncogene. 1999 Aug 5;18(31):4409-15
references.pmid: 10442631
references.citation: Oncogene. 2008 Feb 14;27(8):1155-66
references.pmid: 17700518
references.citation: Oncogene. 2005 Oct 27;24(47):7012-21
references.pmid: 16044159
references.citation: Biochem J. 2005 Sep 15;390(Pt 3):729-35
references.pmid: 15916534
references.citation: Radiother Oncol. 2007 Dec;85(3):371-8
references.pmid: 18035440
references.citation: Cancer Res. 2006 Feb 1;66(3):1491-9
references.pmid: 16452205
references.citation: Dev Cell. 2001 Aug;1(2):239-50
references.pmid: 11702783
references.citation: J Neurochem. 1998 Sep;71(3):1307-14
references.pmid: 9721757
references.citation: J Biol Chem. 2004 Mar 26;279(13):12840-7
references.pmid: 14707138
references.citation: J Biol Chem. 1993 Mar 15;268(8):5911-20
references.pmid: 8449955
references.citation: Cancer Res. 2008 Nov 15;68(22):9302-10
references.pmid: 19010903
references.citation: Mol Cell Biol. 2004 Jun;24(11):5005-15
references.pmid: 15143191
references.citation: Cancer Res. 2001 Feb 1;61(3):1162-70
references.pmid: 11221847
references.citation: Mol Cancer Ther. 2008 May;7(5):1013-24
references.pmid: 18445660
references.citation: J Cell Mol Med. 2008 Dec;12(6A):2416-26
references.pmid: 18284607
references.citation: Mol Cell Biol. 2003 Jul;23(13):4511-21
references.pmid: 12808093
references.citation: J Biol Chem. 2002 Jul 12;277(28):25020-5
references.pmid: 11976344
references.citation: Lancet. 2002 Mar 23;359(9311):1011-8
references.pmid: 11937180
references.citation: Int J Cancer. 2007 Mar 15;120(6):1215-22
references.pmid: 17192900