Endocrine Abstracts

Introduction: Neuroendocrine tumors (NETs) comprise a unique heterogeneous group of malignant growths that range from benign and multi-focal to highly malignant and metastatic. They are characterized by well-differentiated morphologic features and the ability to secrete neuropeptides, resulting in characteristic clinical syndromes. However, they are often diagnosed from the metastases of an unknown primary tumor. Therefore, high-quality genetic and immunohistochemical markers are needed to confirm the diagnosis. Here we conduct integrated genome and immunohistochemistry analysis (IHC) of the DAXX (death domain-associated protein) gene as well as analysis of disease-free survival (DFS) and overall survival (OS) in patients diagnosed with NETs.

Material and methods: The study consisted of 65 patients with NETs. During the study period, 36 patients were diagnosed with neuroendocrine tumors of the lung (L-NETs) and 29 patients with neuroendocrine tumors of the gastroenteropancreatic system (GEP-NETs). Tumor-DNA was isolated from fresh-frozen tumor tissue. The IHC analysis was conducted according to the standard histopathological protocol. The real-time PCR was performed for the DAXX gene.

Results: A total of 24 patients (36.9%) were found with mutations in the DAXX gene. The cumulative number of mutations detected in NETs >3 cm was significantly higher (P<0.001) in comparison to NETs <3 cm. We also found that mutations of the DAXX gene were strongly associated with increased features of malignancy including lymphovascular invasion and higher tumor grade. All patients with the mutated DAXX gene had a shorter DFS (P<0.002) and OS (P<0.003).

Conclusion: Our study identified a significant relation between the genomic profile of the DAXX gene and DFS as well as the OS in patients diagnosed with L-NETs and GEP-NETs. The DAXX molecular alterations influence the malignant potential of L-NETs and GEP-NETs and can predict the malignant progression. Therefore, they could be considered as a possible prognostic stratification tool.