Z Gastroenterol 2004; 42 - P226
DOI: 10.1055/s-2004-831680

Nuclear survivin is a powerful novel prognostic marker in gastroenteropancreatic neuroendocrine tumour disease

P Grabowski 1, S Griß 2, CN Arnold 3, D Hoersch 4, R Göke 5, R Arnold 6, B Heine 7, H Stein 8, M Zeitz 9, H Scherübl 1
  • 1Medizinische Klinik I, Charite Campus Benjamin Franklin
  • 2Med. Klinik I Gastroenterologie Charite Campus Benjamin Frankin
  • 3Abteilung Innere Medizin II, Universtaetsklinikum Freiburg
  • 4Klinikum der Philipps-Universität Marburg
  • 5Klinikum der Philpps-Universität Marburg
  • 6Klinikum der Philipps-Universität Marburg
  • 7Abteilung für Pathologie, Charite- Campus Benjamin Franklin
  • 8Institut für Pathologie Charite- Campus Benjamin Franklin
  • 9Med. Klinik I, Abt. für Gastroenterologie, Infektiologie und Rheumatologie, CBF, Charité - Universitätsmedizin Berlin

Background–Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) represent a rare and rather heterogeneous tumour entity. The growth pattern of GEP-NETs ranges from very slowly to fast growing, aggressive types of tumours. Survivin, a member of the family of apoptosis inhibitors, is a bifunctional protein that suppresses apoptosis and regulates cell division.

Aims–Here we determined the prognostic value of survivin in a series of GEP-NETs.

Patients and Methods–Tumour specimens from 104 patients (38 foregut, 53 midgut, 13 hindgut NETs) were studied immunohistochemically for cytoplasmic and nuclear survivin expression as well as for ki–67 antigen expression. 5-year-follow-up was complete in 89 patients. 29 patients with non-metastatic, well-differentiated GEP-NETs had been curatively treated by surgical or endoscopic tumour resection; therefore they were excluded from statistical analysis of survival. Kaplan-Meier-survival curves were calculated for 60 patients with advanced metastatic GEP-NETs.

Results–No recurrencies or tumour-associated deaths occurred in the 29 patients with localised well-differentiated GEP-NETs. All tumours of this group were negative for nuclear survivin. In the 60 patients with advanced metastatic GEP-NETs 15/60 (25%) tumours were nuclear survivin positive. Those 15 patients had a statistically significant worse prognosis (survival of 8 versus 115 months, p<0.00001). Nuclear survivin expression was strongly correlated with the differentiation grade of the tumour: Only 3/47 well-differentiated tumours displayed nuclear survivin, but 12/13 undifferentiated tumours did so.

Conclusions–Nuclear survivin expression appears to be upregulated during progression of GEP-NETs. The analysis of nuclear survivin expression identifies subgroups in metastatic GEP-NETs with good (survivin-) or with less favorable prognosis (survivin+). We propose that the determination of nuclear survivin expression could be used to individualize therapeutic strategies in GEP-NETs in the future.

Key words

neuroendocrine tumour; survivin; proliferation; prognostic marker