WHO 2004 criteria and CK19 are reliable prognostic markers in pancreatic endocrine tumors

Am J Surg Pathol. 2007 Nov;31(11):1677-82. doi: 10.1097/PAS.0b013e31805f675d.


Background: It is difficult to predict the biologic behavior of pancreatic endocrine tumors in absence of metastases or invasion into adjacent organs. The World Health Organization (WHO) has proposed in 2004 size, angioinvasion, mitotic activity, and MIB1 proliferation index as prognostic criteria. Our aim was to test retrospectively the predictive value of these 2004 WHO criteria and of CK19, CD99, COX2, and p27 immunohistochemistry in a large series of patients with long-term follow-up.

Design: The histology of 216 pancreatic endocrine tumor specimens was reviewed and the tumors were reclassified according to the 2004 WHO classification. The prognostic value of the WHO classification and the histopathologic criteria necrosis and nodular fibrosis was tested in 113 patients. A tissue microarray was constructed for immunohistochemical staining. The staining results were scored quantitatively for MIB1 and semiquantitatively for CK19, COX2, p27, and CD99. The prognostic value of these markers was tested in 93 patients.

Results: The stratification of the patients into 4 risk groups according to the 2004 WHO classification was reliable with regard to both time span to relapse and tumor-specific death. In a multivariate analysis, the CK19 status was shown to be independent of the WHO criteria. By contrast, the prognostic significance of COX2, p27, and CD99 could not be confirmed.

Conclusions: The 2004 WHO classification with 4 risk groups is very reliable for predicting both disease-free survival and the time span until tumor-specific death. CK19 staining is a potential additional prognostic marker independent from the WHO criteria for pancreatic endocrine tumors.

MeSH terms

  • 12E7 Antigen
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / analysis
  • Carcinoma, Islet Cell / chemistry
  • Carcinoma, Islet Cell / diagnosis*
  • Carcinoma, Islet Cell / mortality
  • Carcinoma, Islet Cell / pathology
  • Carcinoma, Islet Cell / surgery
  • Cell Adhesion Molecules / analysis
  • Cyclooxygenase 2 / analysis
  • Disease-Free Survival
  • Female
  • Fibrosis
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Insulinoma / chemistry
  • Insulinoma / diagnosis*
  • Insulinoma / mortality
  • Insulinoma / pathology
  • Insulinoma / surgery
  • Kaplan-Meier Estimate
  • Keratin-19 / analysis*
  • Male
  • Middle Aged
  • Necrosis
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Pancreatic Neoplasms / chemistry
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / surgery
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Recurrence
  • Reproducibility of Results
  • Retrospective Studies
  • Time Factors
  • Tissue Array Analysis
  • Treatment Outcome
  • World Health Organization*


  • 12E7 Antigen
  • Antigens, CD
  • CD99 protein, human
  • Cell Adhesion Molecules
  • Keratin-19
  • Cyclooxygenase 2
  • PTGS2 protein, human