ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 P447 | DOI: 10.1530/endoabs.63.P447

Down-regulation of the Ataxia Telangiectasia Mutated Gene (ATM) is associated with increased metastatic potential and decreased overal survival in patients diagnosed with gastroenteropancreatic neuroendocrine tumors (GEP-NETs)

Darko Katalinic1, Ivan Aleric1, Aleksandar Vcev1, Jure Mirat1, Lilly Soerensen2 & Stephan Bildat3


1Faculty of Medicine and Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; 2Department of Cancer Medicine, Oslo, Norway; 3Herford Teaching Hospital, Medical Campus OWL, Herford, Germany.


Introduction: Neuroendocrine tumors (NETs) are rare tumours that develop in cells of the neuroendocrine system. They comprise a heterogeneous group of neoplasms that range from the benign and multi-focal to the highly malignant and metastatic. Here we conduct itegrated genome and immunohistochemistry analysis (IHC) of the Ataxia Telangiectasia Mutated Gene (ATM) as well as analysis of overal survival in patients diagnosed with NETs.

Material and Methods: The study accrued 65 patients with NETs over a period of 2 years, from 2015 to 2017. During the study period, 36 patients were diagnosed with early and advanced neuroendocrine tumors of the lung (L-NET) and 29 neuroendocrine tumors of the gastroenteropancreatic system (GEP-NET). Tumor-DNA were isolated from fresh-frozen tumor tissue. The IHC-Analysis as well as Real-Time-PCR was performed for ATM-Gene. Survival analysis of the subjects was performed using Kaplan-Meier and Cox regression methods.

Results: We have not found any realations between genomic profile of the ATM-gene and overal survival (OS) in patients diagnosed with L-NET. The down-regulation of the ATM-gene was strongly positively correlated with metastatic GEP-NETs (P<0.001) compared to non-metastatic GEP-NETs (P<0.08). All patients diagnosed with GEP-NETs and with ATM-negativity by IHC, showed decreased OS compared to those with ATM-positivity.

Conclusion: Our study identified that ATM-gene down-regulation was strongly associated with metastatic potential of GEP-NETs. In view of the role played by ATM-gene-expression on the behavior of GEP-NETs and progression of the disease, the ATM-gene negativity could be considered as a possible prognostic stratification tool.