Comparison of tumor markers for predicting outcomes after resection of nonfunctioning pancreatic neuroendocrine tumors

Surgery. 2014 Dec;156(6):1504-10; discussion 1510-1. doi: 10.1016/j.surg.2014.08.043. Epub 2014 Nov 11.

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).

Conclusion: 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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Biomarkers, Tumor / metabolism*
  • Cohort Studies
  • Databases, Factual
  • Disease-Free Survival
  • Female
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism
  • Kaplan-Meier Estimate
  • Keratin-19 / metabolism
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neuroendocrine Tumors / blood*
  • Neuroendocrine Tumors / mortality
  • Neuroendocrine Tumors / surgery
  • Pancreatectomy / methods*
  • Pancreatectomy / mortality
  • Pancreatic Neoplasms / blood*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / surgery
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Proto-Oncogene Proteins c-kit / metabolism
  • ROC Curve
  • Retrospective Studies
  • Survival Analysis
  • Survivin

Substances

  • BIRC5 protein, human
  • Biomarkers, Tumor
  • Inhibitor of Apoptosis Proteins
  • Keratin-19
  • Ki-67 Antigen
  • Survivin
  • Proto-Oncogene Proteins c-kit

Supplementary concepts

  • Non functioning pancreatic endocrine tumor