Endocrine tumors of the pancreas: Ki-67 immunoreactivity on paraffin sections is an independent predictor for malignancy: a comparative study with proliferating-cell nuclear antigen and progesterone receptor protein immunostaining, mitotic index, and other clinicopathologic variables

Hum Pathol. 1996 Nov;27(11):1124-34. doi: 10.1016/s0046-8177(96)90303-2.


Prediction for malignancy of pancreatic endocrine tumors (PET) is often a formidable challenge for the pathologist. The authors evaluated the role of the proliferative activity and progesterone receptor protein (PgRP) in predicting prognosis and survival of PET. Twenty-three functioning (FT) and 31 nonfunctioning tumors (NFT) were evaluated for mitotic activity and immunostaining for Ki-67 antigen, proliferating cell nuclear antigen (PCNA), and progesterone receptor protein (PgRP) on paraffin sections. The results were expressed as a percentage (index) of immunoreactive or mitosing cells. All 54 cases showed immunostaining for Ki-67 and PCNA, and valuable mitotic index, whereas only a fraction of tumors (25 of 54 cases) exhibited PgRP expression. Ki-67 and PCNA indexes correlated strongly between themselves and to mitotic index, whereas an inverse relationship was observed between cell proliferation and PgRP status in both FT and NFT. Although univariate analysis showed that Ki-67, PCNA, mitotic and PgRP indexes, stage, immunoreactivity for hormones other than insulin, diameter, and nonfunctioning type of tumor were statistically correlated to survival, Cox's regression method let only Ki-67 index emerge as an independent predictor of survival using a cutoff value of 5% in both FT and NFT.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma, Islet Cell / diagnosis*
  • Adenoma, Islet Cell / immunology
  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis*
  • Male
  • Middle Aged
  • Mitotic Index*
  • Multivariate Analysis
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / immunology
  • Proliferating Cell Nuclear Antigen / analysis*
  • Receptors, Progesterone / analysis*
  • Retrospective Studies
  • Survival Rate
  • Treatment Outcome


  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Proliferating Cell Nuclear Antigen
  • Receptors, Progesterone