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- 저자 : Brosnan-Cashman, Jacqueline A. (검색결과 1 건)
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Kim, Joo Young,Brosnan-Cashman, Jacqueline A.,An, Soyeon,Kim, Sung Joo,Song, Ki-Byung,Kim, Min-Sun,Kim, Mi-Ju,Hwang, Dae Wook,Meeker, Alan K.,Yu, Eunsil,Kim, Song Cheol,Hruban, Ralph H.,Heaphy, Christ American Association for Cancer Research 2017 Clinical Cancer Research Vol.23 No.6
<P><B>Purpose:</B> Alternative lengthening of telomeres (ALT), a telomerase-independent telomere maintenance mechanism, is strongly associated with ATRX and DAXX alterations and occurs frequently in pancreatic neuroendocrine tumors (PanNET).</P><P><B>Experimental Design:</B> In a Korean cohort of 269 surgically resected primary PanNETs and 19 sporadic microadenomas, ALT status and nuclear ATRX and DAXX protein expression were assessed and compared with clinicopathologic factors.</P><P><B>Results:</B> In PanNETs, ALT or loss of ATRX/DAXX nuclear expression was observed in 20.8% and 19.3%, respectively, whereas microadenomas were not altered. ALT-positive PanNETs displayed a significantly higher grade, size, and pT classification (all, <I>P</I> < 0.001). ALT also strongly correlated with lymphovascular (<I>P</I> < 0.001) and perineural invasion (<I>P</I> = 0.001) and the presence of lymph node (<I>P</I> < 0.001) and distant metastases (<I>P</I> = 0.002). Furthermore, patients with ALT-positive primary PanNETs had a shorter recurrence-free survival [HR = 3.38; 95% confidence interval (CI), 1.83–6.27; <I>P</I> < 0.001]. Interestingly, when limiting to patients with distant metastases, those with ALT-positive primary tumors had significantly better overall survival (HR = 0.23; 95% CI, 0.08–0.68; <I>P</I> = 0.008). Similarly, tumors with loss of ATRX/DAXX expression were significantly associated with ALT (<I>P</I> < 0.001), aggressive clinical behavior, and reduced recurrence-free survival (<I>P</I> < 0.001). However, similar to ALT, when limiting to patients with distant metastases, loss of ATRX/DAXX expression was associated with better overall survival (<I>P</I> = 0.003).</P><P><B>Conclusions:</B> Both primary ALT-positive and ATRX/DAXX-negative PanNETs are independently associated with aggressive clinicopathologic behavior and displayed reduced recurrence-free survival. In contrast, ALT activation and loss of ATRX/DAXX are both associated with better overall survival in patients with metastases. Therefore, these biomarkers may be used as prognostic markers depending on the context of the disease. <I>Clin Cancer Res; 23(6); 1598–606. ©2016 AACR</I>.</P>
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