Changing biological behaviour of NETs during the evolution of the disease: progress on progression

in Endocrine-Related Cancer
View More View Less
  • 1 K Alexandraki, Endocrine Unit, First Department of Propaedeutic Medicine, Laiko University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
  • 2 A Spyroglou, First Department of Propaedeutic Medcine, Laiko University Hospital, National and Kapodistrian University of Athens, Athens, Greece
  • 3 S Kykalos, Second Department of Propaedeutic Surgery, National and Kapodistrian University of Athens, Athens, Greece
  • 4 K Daskalakis, Endocrine Unit, First Department of Propaedeutic Medicine, Laiko University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
  • 5 G Kyriakopoulos, Department of Pathology, Evaggelismos Hospital, Athens, Greece
  • 6 G Sotiropoulos, Second Department of Propaedeutic Surgery, Medical School, National and Kapodistrian University of Athens, Athens, Greece
  • 7 G Kaltsas, Endocrine Unit, First Department of Propaedeutic Medicine, Laiko University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
  • 8 A Grossman, Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford University, Oxford, United Kingdom of Great Britain and Northern Ireland

Correspondence: Krystallenia Alexandraki, Email: alexandrakik@gmail.com
Restricted access

Following improvements in the management and outcome of neuroendocrine neoplasms (NENs) in recent years, we see a subset, particularly of pancreatic NENs, which become more aggressive during the course of the disease. This is reflected by an increase in the Ki-67 labelling index, as a marker of proliferation, which may lead on occasion to an increase in grading, but generally does not appear to be correlated with histologically confirmed de-differentiation. A systematic review of the literature was performed in PubMed, Cochrane Library, and Embase until May 2020 to identify cases that have behaved in such a manner. We screened 244 articles: only 7 studies included cases in their cohort, or in a subset of the cohort studied, with a proven increase in the Ki-67 during follow-up through additional biopsy. In addition to these studies, we have also tried to identify possible pathophysiological mechanisms implicated in advanced NENs, although currently no studies appear to have addressed the mechanisms implicated in the switch to a more aggressive biological phenotype over the course of the disease. Such progression of the disease course may demand a change in management. Summarising the evidence overall, we suggest that future studies should concentrate on changes in molecular pathways during disease progression with sequential biopsies in order to shed light on the mechanisms that render a neoplasm more aggressive than its initial phenotype or genotype.

 

Society for Endocrinology