Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2014 Jun;38(6):1353-61.
doi: 10.1007/s00268-014-2451-0.

Role of Ki-67 Proliferation Index in the Assessment of Patients With Neuroendocrine Neoplasias Regarding the Stage of Disease

Comparative Study

Role of Ki-67 Proliferation Index in the Assessment of Patients With Neuroendocrine Neoplasias Regarding the Stage of Disease

H C Miller et al. World J Surg. .


Background: Neuroendocrine neoplasias (NEN) of the gastroenteropancreatic (GEP) system frequently present with metastatic deposits. The proliferation marker Ki-67 is used for diagnosis and to assess the prognosis of disease. The aim of our study was to evaluate the usefulness of Ki-67 % in the assessment of NEN patients with regard to their disease stage in clinical practice. Additionally, a comparative analysis of Ki-67 levels among different sites of disease was performed.

Methods: This retrospective study included patients with GEP NEN referred to our center from 2010 to 2012. The NEN diagnosis was confirmed by standard histopathology. Ki-67 immunohistochemistry was done on paraffin-embedded sections using an automated Leica immunohistochemistry machine. NEN grading was carried out according to European Neuroendocrine Tumor Society recommendations (low grade [G1] to intermediate grade [G2], well to moderately differentiated neuroendocrine neoplasms; high-grade [G3], moderately to poorly differentiated neuroendocrine neoplasms). Results of tumor staging and grading were correlated. In a subgroup of cases, comparative analysis of Ki-67 levels in different sites of disease was carried out.

Results: One hundred sixty-one GEP NEN patients were included in the study. Metastatic disease was seen in 46.1 % (53/115) of G1 tumors, 77.8 % (28/36) of G2 tumors, and 100 % of (10/10) G3 tumors (p = 0.0002). When stratified according to primary tumor site, metastatic disease was documented in 42.9 % (36/84) of patients with pancreatic NEN and in 91.9 % (34/37) of those with small intestinal primary. Stage IV metastatic disease was present in 27.8 % (32/115) and 72.2 % (26/36) of the G1 and G2 tumors, respectively, and in 90 % (9/10) of the G3 tumors. Assessment of the Ki-67 index for a subset of cases at metastatic sites as well as the primary tumor site showed discrepancies in 35.3 % cases. In 7/9 (77.8 %) patients with liver metastases, Ki-67 % was higher in the liver lesions than in the primary tumor.

Conclusions: Patients with GEP NEN exhibiting a high Ki-67 proliferation index present with metastatic disease in the vast majority of cases. Depending upon the primary tumor site, metastases are to be expected also in tumors with low Ki-67 %, although they are considered less aggressive. Different disease sites may express heterogeneous Ki-67 levels.

Similar articles

See all similar articles

Cited by 23 articles

See all "Cited by" articles


    1. Semin Nucl Med. 2012 May;42(3):190-207 - PubMed
    1. Br J Surg. 2009 Feb;96(2):175-84 - PubMed
    1. Neuroendocrinology. 2012;95(2):157-76 - PubMed
    1. Virchows Arch. 2006 Oct;449(4):395-401 - PubMed
    1. N Engl J Med. 2011 Feb 10;364(6):501-13 - PubMed

Publication types

MeSH terms

LinkOut - more resources