Impact of Ki67 re-assessment at time of disease progression in patients with pancreatic neuroendocrine neoplasms

PLoS One. 2017 Jun 23;12(6):e0179445. doi: 10.1371/journal.pone.0179445. eCollection 2017.

Abstract

Background: Although re-assessment of proliferative activity by K67 evaluation during the course of neuroendocrine neoplasms (NENs) is recommended in selected patients, its impact on patients' management is not clear due to the lack of data supporting this practice.

Aim: To investigate Ki67 change at time of progressive disease (PD) in entero-pancreatic NENs (EP-NENs).

Patients and methods: Retrospective analysis of sporadic EP-NENs which received histological re-assessment after PD once radiologically documented.

Results: Forty-three patients were evaluated, including 24 pancreatic NENs (PNENs), and 19 small intestine NENs (SI-NENs). At time of initial histological evaluation, 19 patients had grade 1 (G1) NETs (44.2%), and 24 grade 2 (G2) NETs (55.8%), overall median Ki67 being 3% (range 1%-20%). At time of PD, 13 patients had G1 NETs (30.2%), 26 G2 NETs (60.5%), and 4 had grade 3 (G3) NECs (9.3%), thus resulting in a significant median Ki67 increase (8%, range 1%-70%; p = 0.0006), and a G upgrading in 12 patients (27.9%). A statistically significant Ki67 increase and G grading change at time of PD was observed in PNENs (p = 0.0005 and p = 0.028, respectively). Conversely, no statistically significant change occurred in non-PNENs.

Conclusions: In PNENs with documented PD, Ki67 increase occurs in a significant proportion of patients, providing useful information necessary to choose appropriate therapeutic options.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Disease Progression
  • Female
  • Humans
  • Ki-67 Antigen / metabolism*
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Neuroendocrine Tumors / diagnostic imaging
  • Neuroendocrine Tumors / metabolism*
  • Neuroendocrine Tumors / pathology
  • Pancreatic Neoplasms / diagnostic imaging
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Retrospective Studies
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen

Grants and funding

This work was supported by AIRC grant IG 2015, Id 17177. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.