title: Prognostic relevance of survivin in pancreatic endocrine tumors.
abstract: BACKGROUND
  Better prognostic markers are needed for pancreatic endocrine tumors. Survivin is an apoptosis inhibitor that is suggested to have a negative prognostic impact in several tumor types. Contradictory data exist, especially regarding the significance of a nuclear versus cytoplasmic location of survivin. The prognostic relevance of nuclear and cytoplasmic survivin expression in pancreatic endocrine tumors-controlled for the tumor Ki-67 index, World Health Organization classification, and TNM stage-was investigated.
  
  
  METHODS
  A total of 111 patients treated at a tertiary referral center were retrospectively evaluated. Clinical data were gathered from medical records. Immunohistochemistry for survivin and Ki-67 was performed on paraffin-embedded tissue. Univariate and multivariate Cox analyses were performed.
  
  
  RESULTS
  Patients with tumors that had <5% survivin-positive nuclei had a mean survival of 225 months [95% confidence interval (CI) 168-281]. The corresponding figure for patients with 5 to 50% survivin-positive tumor cell nuclei was 101 months [95% CI 61-140; hazard ratio (HR) 2.4; P < 0.01) and with >50% survivin-positive nuclei 47 months (95% CI 24-71; HR 4.9; P < 0.001). Nuclear survivin expression in >50% of the tumor cells was an independent marker of a poor prognosis (HR 5.7; P < 0.01). Cytoplasmic survivin was not a significant prognostic factor in the multivariate analysis (HR 0.94; P = 0.90).
  
  
  CONCLUSIONS
  High expression of nuclear survivin is a significant marker of a poor prognosis in patients with a pancreatic endocrine tumor.
authors.affiliation: Department of Medical Sciences, Uppsala University, 751 85 Uppsala, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Ekeblad
authors.forename: Margareta Halin
authors.initials: MH
authors.lastname: Lejonklou
authors.forename: Peter
authors.initials: P
authors.lastname: Stålberg
authors.forename: Britt
authors.initials: B
authors.lastname: Skogseid
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018273:Carcinoma, Islet Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D007340:Insulinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D015996:Survival Rate; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D000077022:Survivin
references.citation: Cancer Lett. 2001 Feb 10;163(1):109-16
references.pmid: 11163114
references.citation: Ann N Y Acad Sci. 2004 Apr;1014:222-33
references.pmid: 15153439
references.citation: Curr Opin Cell Biol. 2006 Dec;18(6):616-22
references.pmid: 16962308
references.citation: Br J Cancer. 2005 Jun 20;92(12):2225-32
references.pmid: 15928668
references.citation: Clin Cancer Res. 2008 Dec 1;14(23):7798-803
references.pmid: 19047107
references.citation: Neuroendocrinology. 2005;81(1):1-9
references.pmid: 15809513
references.citation: Br J Surg. 2008 May;95(5):627-35
references.pmid: 18306152
references.citation: J Clin Oncol. 2002 Jun 1;20(11):2633-42
references.pmid: 12039924
references.citation: Curr Opin Cell Biol. 2006 Dec;18(6):609-15
references.pmid: 16934447
references.citation: EMBO J. 2003 Jun 2;22(11):2729-40
references.pmid: 12773388
references.citation: Expert Opin Ther Targets. 2008 Apr;12(4):463-76
references.pmid: 18348682
references.citation: Mol Cancer. 2011 Apr 06;10:35
references.pmid: 21470426
references.citation: Nat Genet. 1999 Dec;23(4):387-8
references.pmid: 10581018
references.citation: Virchows Arch. 1996 Dec;429(6):323-33
references.pmid: 8982376
references.citation: Hum Pathol. 1996 Nov;27(11):1124-34
references.pmid: 8912819
references.citation: Endocr Pathol. 1997 Autumn;8(3):181-187
references.pmid: 12114721
references.citation: J Biol Chem. 2006 Jan 13;281(2):1286-95
references.pmid: 16291752
references.citation: Ann N Y Acad Sci. 2004 Apr;1014:13-27
references.pmid: 15153416
references.citation: Ann Oncol. 2005 Nov;16(11):1806-10
references.pmid: 16085691
references.citation: Genes Dev. 1999 Feb 1;13(3):239-52
references.pmid: 9990849
references.citation: Oncogene. 2005 Mar 17;24(12):1994-2007
references.pmid: 15688031
references.citation: Endocr Relat Cancer. 2005 Dec;12(4):1083-92
references.pmid: 16322345
references.citation: Virchows Arch. 2006 Oct;449(4):395-401
references.pmid: 16967267
references.citation: Hum Pathol. 2006 Jul;37(7):802-8
references.pmid: 16784978
references.citation: Br J Cancer. 2003 Apr 7;88(7):1077-83
references.pmid: 12671708
references.citation: Cell Death Differ. 2002 Dec;9(12):1334-42
references.pmid: 12478470
references.citation: Biochem Biophys Res Commun. 2004 Feb 13;314(3):902-7
references.pmid: 14741722
references.citation: Br J Cancer. 2004 Aug 2;91(3):537-40
references.pmid: 15266313
references.citation: Mod Pathol. 2004 Nov;17(11):1378-85
references.pmid: 15195112
references.citation: Oncogene. 1998 Dec 24;17(25):3247-59
references.pmid: 9916987