Evidence map›Paper›PMID 24655849›Full record

ArticleJournal of the American College of Surgeons2014

Alternative lengthening of telomeres predicts site of origin in neuroendocrine tumor liver metastases.

Epameinondas Dogeas, Georgios Karagkounis, Christopher M Heaphy, Kenzo Hirose, Timothy M Pawlik, Christopher L Wolfgang, Alan Meeker, Ralph H Hruban, John L Cameron, Michael A Choti

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In one paragraph

Article in Journal of the American College of Surgeons, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  13. Incidentally detected pancreatic neuroendocrine microadenoma with lymph node metastasis.Virchows Archiv : an international journal of pathology · 2018
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  16. Alternative Lengthening of Telomeres in Primary Pancreatic Neuroendocrine Tumors Is Associated with Aggressive Clinical Behavior and Poor Survival.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Epameinondas DogeasDepartment of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD.
Georgios KaragkounisDepartment of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD.
Christopher M HeaphyDepartment of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD.
Kenzo HiroseDepartment of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD.
Timothy M PawlikDepartment of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD.
Christopher L WolfgangDepartment of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD.
Alan MeekerDepartment of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD.
Ralph H HrubanDepartment of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD.
John L CameronDepartment of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD.
Michael A ChotiDepartment of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD; Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX. Electronic address: michael.choti@utsouthwestern.edu.

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6M
NCI NIH HHS P30 CA006973
6 · The paper itself

Abstract

backgroundThe determination of the primary tumor origin in patients with neuroendocrine tumor liver metastases (NELM) can pose a considerable management challenge. Recent studies have shown that the alternative lengthening of telomeres (ALT) is prevalent in some human tumors, including pancreatic neuroendocrine tumors (PanNET), and can be useful in predicting tumor biology. In this study, we aimed to evaluate the use of ALT as a biomarker in patients with NELM, in particular to predict the site of origin of metastases.

methodsTissue microarrays (TMAs) were constructed using tumor tissue from NELM patients undergoing liver resection between 1998 and 2010. These included 43 PanNET and 47 gastrointestinal carcinoid tumors. The TMAs were tested for ALT using telomere-specific fluorescent in situ hybridization. The association between ALT positivity and clinicopathologic features and long-term outcomes was investigated.

resultsAlternative lengthening of telomeres was positive (ALT+) in 26 (29%) of the 90 tumors included in the TMAs. Pancreatic neuroendocrine tumors were ALT+ in 56% of patients, compared with only 4% ALT+ among gastrointestinal carcinoid tumors (p < 0.001). The specificity of ALT for detecting pancreatic origin was 96% and the positive predictive value was 92%, and sensitivity was 56% and the negative predictive value was 70%. Additionally, ALT was associated with the pattern of metastatic disease: ALT+ NELM were more likely to have oligometastases (p = 0.001) and less likely to be bilateral in distribution (p = 0.05) than were ALT tumors. In addition, ALT+ was associated with improved prognosis in the PanNET patient population.

conclusionsAlternative lengthening of telomeres was found to be a useful biomarker in patients with NELM. This marker can be helpful in guiding therapy by identifying the site of origin in patients in whom the primary site is unknown.

Indexed as

Telomere HomeostasisAdolescentAdultAgedAged, 80 and overFemaleGastrointestinal NeoplasmsGenetic MarkersHepatectomyHumansIn Situ Hybridization, FluorescenceLiver NeoplasmsMaleMiddle AgedNeuroendocrine TumorsPancreatic NeoplasmsGenetic Markers

Identifiers

PMID24655849
PMCPMC4332797

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.