Original Article

Evaluation of Gastroenteropancreatic Neuroendocrine Tumors for Ki 67, p16 and Cyclin D1 Expression


  • Gülzade ÖZYALVAÇLI
  • Zuhal GÜCİN
  • Feray GÜNVER
  • Erol Rüştü BOZKURT

Received Date: 14.04.2011 Accepted Date: 05.07.2011 İstanbul Med J 2011;12(3):105-112


The aim of this study was to examine the roles of p16/cyclin D1 and Ki 67 proliferation index in gastroenteropancreatic neuroendocrine tumors (GEPNETs), which were classified by the World Health Organization (WHO).


A series of 41 cases of GEPNETs including 16 well-differentiated endocrine tumors (WDET), 17 welldifferentiated endocrine carcinomas (WDEC) and 8 poorly differentiated endocrine carcinomas (PDEC) were searched for p16, cyclin D1 and Ki 67 expression.


Overexpression of p16 and cyclin D1 was observed in 8 (50%) and 8 (50%) of 16 WDET cases, 12 (70%) and 5 (29%) of 17 WDEC cases and 5 (63%) and 5 (63%) of 8 PDEC cases. Low Ki 67 index (≤2%) was found in 15 (94%) of WDETs, 13 (76%) of WDECs and none of PDECs.


Ki 67 index was low in WDECs as in WDETs. High Ki 67 index (>10%) is related to poor prognosis, but low proliferation activity is not an indicator of benign behavior. There were no significant differences between the tumor groups with respect to p16 and cyclin D1 expression in our study. More objective results can be obtained in such studies that include retinoblastoma protein and analyze all of the components of the Rb pathway.

Keywords: Cyclin D1, GEPNET, Ki 67 index, p16