Abstract
Neuroendocrine tumors (NETs) are a heterogenous group of tumors. While most NETs have excellent prognosis, certain subsets have aggressive biology and have limited treatment options. We explored the role of survivin in NET as a prognostic and potentially therapeutic marker. Tissue microarrays of 132 patients were stained for survivin using immunohistochemistry (IHC) and correlated with outcomes. Using genomic database, we then correlated survivin (BIRC5) mRNA expression with radiosensitivity index (RSI) in 52 samples of NET. Finally, we studied the effect of radiation on survivin expression in human cell lines and the impact of knock-down of BIRC5 on cell proliferation and radiation sensitivity. We found that survivin positivity by IHC correlated with a shorter survival (overall survival 8.5 years vs. 18.3 years, p < 0.001). There was a positive correlation between BIRC5 expression and RSI (r = 0.234, p < 0.0001). Radiation exposure increased BIRC5 gene expression in a human carcinoid cell line. Knockout of BIRC5 using siRNA reduced proliferation of neuroendocrine cells but did not increase radiation sensitivity. We conclude that survivin expression in NET correlates with an inferior survival and survivin expression in human carcinoid cell lines increases after exposure to ionizing radiation.
Highlights
Neuroendocrine tumors (NET) are a heterogeneous group of neoplasms that arise from neuroendocrine cells or their precursors
We examined the survivin mRNA (BIRC5) expression and radiosensitivity index (RSI) in lung NET as well as non-cancerous lung tissue (n = 10) using data deposited in Gene Expression Omnibus (GEO) database by Asiedu et al Within this limited dataset, we found a non-significant trend of increasing BIRC5 mRNA expression with progressive dysplasia in lung NET in the order of non-cancerous lung tissues, typical carcinoid and atypical carcinoid (Figure 4B)
Our results show that survivin is associated with aggressive tumor biology as reflected by higher grade and correlation with Ki-67 index, as well as inferior prognosis manifesting as a shorter overall survival
Summary
Neuroendocrine tumors (NET) are a heterogeneous group of neoplasms that arise from neuroendocrine cells or their precursors. They are considered rare cancers, but the incidence has increased over the last 30 years to 6.98 cases per 100,000 population per year [1, 2]. Classification of NET range from well-differentiated neuroendocrine tumors to poorly differentiated neuroendocrine carcinomas (NEC) based on their morphology and histological grade assessed by Ki-67 proliferation index or number of mitoses per 10 high-powered fields [3]. Lung NET are generally more aggressive and are associated with a worse overall survival of around 17 months. Novel immunotherapy and biomarker selected studies / rational combinations are needed
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
