title: Comparison of tumor markers for predicting outcomes after resection of nonfunctioning pancreatic neuroendocrine tumors.
abstract: BACKGROUND
  This study compares the predictability of 5 tumor markers for distant metastasis and mortality in pancreatic neuroendocrine tumors (PNETs).
  
  
  METHODS
  A total of 128 patients who underwent pancreatectomy for nonfunctioning PNETs between 1998 and 2011 were evaluated. Tumor specimens were stained via immunochemistry for cytoplasmic and nuclear survivin, cytokeratin 19 (CK19), c-KIT, and Ki67. Univariate and multivariate regression analyses and receiver operating characteristics curve were used to evaluate the predictive value of these markers.
  
  
  RESULTS
  A total of 116 tumors (91%) were positive for cytoplasmic survivin, 95 (74%) for nuclear survivin, 85 (66.4%) for CK19, 3 for c-KIT, and 41 (32%) for Ki67 >3%. Twelve (9%) tumors expressed none of the markers. Survivin, CK19, and c-KIT had no substantial effect on distant metastasis or mortality. Age >55 years, grade 3 histology, distant metastasis, and Ki67 >3% were associated with mortality (P < .05). A cut-off of Ki67 >3% was the best predictor (83%) of mortality with an area under the curve of 0.85. Ki67 >3% also predicted occurrence of distant metastases with odds ratio of 9.22 and 95% confidence interval of 1.55-54.55 (P < .015).
  
  
  CONCLUSIONS
  Of the 5 markers studied, only Ki67 >3% was greatly associated with distant metastasis and death. Survivin, CK19, and c-KIT had no prognostic value in nonfunctioning PNETs.
authors.forename: Jovenel
authors.initials: J
authors.lastname: Cherenfant
authors.forename: Mark S
authors.initials: MS
authors.lastname: Talamonti
authors.forename: Curtis R
authors.initials: CR
authors.lastname: Hall
authors.forename: Tiffany A
authors.initials: TA
authors.lastname: Thurow
authors.forename: Mistry K
authors.initials: MK
authors.lastname: Gage
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Stocker
authors.forename: Brittany
authors.initials: B
authors.lastname: Lapin
authors.forename: Edward
authors.initials: E
authors.lastname: Wang
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Silverstein
authors.forename: Kathy
authors.initials: K
authors.lastname: Mangold
authors.forename: Melanie
authors.initials: M
authors.lastname: Odeleye
authors.forename: Karen L
authors.initials: KL
authors.lastname: Kaul
authors.forename: Ihab
authors.initials: I
authors.lastname: Lamzabi
authors.forename: Paolo
authors.initials: P
authors.lastname: Gattuso
authors.forename: David J
authors.initials: DJ
authors.lastname: Winchester
authors.forename: Robert W
authors.initials: RW
authors.lastname: Marsh
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Roggin
authors.forename: David J
authors.initials: DJ
authors.lastname: Bentrem
authors.forename: Marshall S
authors.initials: MS
authors.lastname: Baker
authors.forename: Richard A
authors.initials: RA
authors.lastname: Prinz
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015331:Cohort Studies; D016208:Databases, Factual; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D053539:Keratin-19 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018358:Neuroendocrine Tumors / Q000097:blood* / Q000401:mortality / Q000601:surgery; D010180:Pancreatectomy / Q000379:methods* / Q000401:mortality; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000401:mortality / Q000601:surgery; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012372:ROC Curve; D012189:Retrospective Studies; D016019:Survival Analysis; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D053539:Keratin-19; D019394:Ki-67 Antigen; D000077022:Survivin; D019009:Proto-Oncogene Proteins c-kit