Pancreatic endocrine tumors: new putative prognostic markers and therapeutic targets

Background. Pancreatic endocrine tumor (PET) is a heterogeneous group of neoplasms which have usually a better prognosis compared to the ductal adenocarcinoma but can also progress to more aggressive form. Currently, little is know about the biological mechanism behind PET development and progression, partly due to the relative rarity of the disease. Using gene expression profile, we analyzed a panel of samples generating the largest study on PET transcriptome, to date. Methods and results. The expression profiles of 72 primary tumors, seven matched metastases and ten normal samples were analyzed. Relevant differentially expressed genes were validated by either quantitative RT-PCR or immunohistochemistry on tissue microarrays. Our analysis showed that: i) tuberin and PTEN proteins, two key inhibitors of Akt/mTOR pathway, were down-regulated in most of the primary tumors and their low expression was associated with shorter disease-free survival and overall survival; ii) somatostatin receptor 2 protein was absent or poorly expressed in insulinomas compared to non-functioning PETs; iii) expression of fibroblast growth factor 13 gene was associated with the occurrence of liver metastasis and shorter disease-free survival. Conclusions. The main strength of this paper is its potential impact in pancreatic endocrine tumor therapy. Several drugs that inhibit PI3K and mTOR have reached phase I or II clinical trials in other tumor types, and our work suggests that they could be relevant for treating PET. In addition, we identified a new prognostic marker which predicted poorer outcome in patients who were clinically considered free from disease.