Nuclear survivin is a prognosticator in gastroenteropancreatic neuroendocrine neoplasms: a meta-analysis

Abstract

Purpose: Gastroenteropancreatic neuroendocrine neosplasms (GEP-NEN) are biologically heterogenous tumors with an increasing incidence over the past decades. Although efforts have been made in the treatment of these tumors, survival rates in metastasized tumor stages remain frustrating. Thus, there is an urgent need to identify novel targets as alternative treatment options. In this regard, the inhibitor of apoptosis protein (IAP) family member survivin could be such an attractive target. Therefore, aim of our meta-analysis was to assess the role of survivin as a biomarker and predictor in GEP-NEN. Methods: Medline, Web of Science and Scopus were screened for studies that fulfilled our selection criteria. Quality assessement of the studies was based on design, methodology, generalizability and results analysis. Meta-analyses were conducted using a random-effects model and effect size measures were expressed as pooled Hazard Ratio (HR) or Odds Ratio (OR) with 95% Confidence Interval (CI). Results: Six eligible studies with 649 patients (range 77–132) assessed survivin expression in GEP-NEN by immunohistochemistry. High expression levels of nuclear survivin in GEP-NEN correlated with a shorter overall survival (HR 3.10; 95% CI 2.15–4.47; p < 0.0001). In contrast to cytoplasmic survivin (OR 1.24; CI 0.59–2.57; p = 0.57), nuclear survivin was also associated (OR 15.23; CI 3.61–64.23; p = 0.0002) with G3/poorly differentiated GEP-NEN. Conclusion: Nuclear Survivin is highly expressed in more aggressive G3 GEP-NEN and correlates with a poor outcome. Survivin is therefore an interesting molecule for a targeted therapy, especially for patients with highly proliferative G3 GEP-NENs.