Oncotarget

Research Papers:

DAXX/ATRX and MEN1 genes are strong prognostic markers in pancreatic neuroendocrine tumors

Joo Kyung Park, Woo Hyun Paik, Kyoungbun Lee, Ji Kon Ryu _, Sang Hyub Lee and Yong-Tae Kim

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Oncotarget. 2017; 8:49796-49806. https://doi.org/10.18632/oncotarget.17964

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Abstract

Joo Kyung Park1,*, Woo Hyun Paik2,*, Kyoungbun Lee3,*, Ji Kon Ryu2, Sang Hyub Lee2 and Yong-Tae Kim2

1Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

2Department of Internal Medicine and Liver Research Institutute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea

3Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea

*These authors contributed equally to this work

Correspondence to:

Ji Kon Ryu, email: jkryu@snu.ac.kr

Keywords: DAXX/ATRX, MEN, neuroendocrine tumor

Received: April 30, 2016     Accepted: May 01, 2017     Published: May 18, 2017

ABSTRACT

Background: PanNETs shows heterogeneous biological behaviors. The aim was to investigate prognostic markers based on most frequently mutated genes in PanNETs.

Results: There was a total of 76 patients (M: 39, F: 37) with pathologically proven PanNETs. ATRX/DAXX and MEN1 protein expression was detected in 16 (21%) and 31 (41%) patients, respectively. The mean OS of the total study patients was 16 years, and DFS was 17 years among the 68 patients with curative resections. PanNETs presented with distant metastasis or loss of ATRX/DAXX protein expression was the independent prognostic factors associated with poor OS. In curative resected PanNETs, there was no significant difference in the mean DFS according to ATRX/DAXX or MEN1 protein. However, there was statistically significant difference in survival after the recurrence according to the expression of ATRX/DAXX protein; Y/N: 10 vs. 15 years, p < 0.001. In metastatic PanNETs, we could find out OS was significantly longer in negative protein expression of ATRX/DAXX and MEN1 groups; 7 vs. 1 years, p < 0.001, 6 vs. 2 years, p = 0.02, respectively.

Materials and Methods: The histologically proven PanNETs were enrolled and the clinicopathologic and genetic alterations were evaluated.

Conclusions: Protein expression of MEN1 and DAXX/ATRX can be prognostic markers for PanNETs. Further investigation in genetic alterations of PanNETs may give us insights understanding the behavior of PanNETs.


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