Evidence map›Paper›PMID 31846235›Full record

ArticleDiagnostic cytopathology2020

Assessment of ARX expression, a novel biomarker for metastatic risk in pancreatic neuroendocrine tumors, in endoscopic ultrasound fine-needle aspiration.

Wenzel M Hackeng, Folkert H M Morsink, Leon M G Moons, Christopher M Heaphy, G Johan A Offerhaus, Koen M A Dreijerink, Lodewijk A A Brosens

Open access · hybridAbstract read
In one paragraph

Article in Diagnostic cytopathology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 11% of its field
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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 2 countries.

Wenzel M HackengDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.ORCID https://orcid.org/0000-0001-6795-179X
Folkert H M MorsinkDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Leon M G MoonsDepartment of Gastroenterology, University Medical Center Utrecht, Utrecht, The Netherlands.
Christopher M HeaphyDepartment of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
G Johan A OfferhausDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Koen M A DreijerinkDepartment of Endocrinology and Internal Medicine, Amsterdam University Medical Center, Amsterdam, The Netherlands.
Lodewijk A A BrosensDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
University Medical Center Utrecht · NLAmsterdam University Medical Centers · NLJohns Hopkins University · USUtrecht University · NL

Funding

Maag Lever Darm Stichting CDG 14-020
6 · The paper itself

Abstract

backgroundThe transcription factors ARX and PDX1, and alternative lengthening of telomeres (ALT) were recently described as prognostic markers for resected non-functional pancreatic neuroendocrine tumors (PanNETs). ALT positive tumors with ARX expression relapse most often. Currently, tumor size is the only preoperative marker used to decide whether or not to operate, thus additional preoperative prognostic markers are needed. Therefore, it is critical to assess the performance of these biomarkers on preoperative cytologic specimens.

methodsEndoscopic fine-needle aspiration cellblock material and corresponding surgical specimens of 13 patients with PanNETs were assessed for histology, immunohistochemical staining of ARX, PDX1, Synaptophysin, Ki67, and telomere-specific fluorescence in situ hybridization to detect ALT, and then associated with clinicopathological features. Scoring for ARX and PDX1 was performed blinded by two independent observers.

resultsOf the 13 surgical specimens, 8 were ARX+/PDX1-, 2 ARX-/PDX1+, and 3 ARX+/PDX1+. Concordance between cytologic and surgical specimens for ARX protein expression was 100%, whereas concordance for PDX1, ALT, and WHO tumor grade was 85%, 91%, and 73%, respectively. There was a perfect inter-observer agreement in ARX and PDX1 scoring.

conclusionARX can reliably be determined in cytologic specimens and has low inter-observer variability. For cytology, false-positive PDX1 expression was observed, possibly due to contamination or sampling, while ALT had a false-negative case due to incomplete sampling. As previously observed, tumor grade is underestimated in cytologic specimens. Thus, ARX and ALT are the most promising markers to predict metastatic behavior in PanNETs, thereby warranting further validation in larger studies.

Indexed as

Gene Expression RegulationAdultAgedBiomarkers, TumorEndoscopic Ultrasound-Guided Fine Needle AspirationFemaleHomeodomain ProteinsHumansMaleMiddle AgedNeoplasm MetastasisNeoplasm ProteinsNeuroendocrine TumorsPancreatic NeoplasmsPreoperative CareTrans-ActivatorsARX protein, humanBiomarkers, TumorHomeodomain ProteinsNeoplasm Proteinspancreatic and duodenal homeobox 1 proteinTrans-ActivatorsTranscription Factorscytologyendoscopic ultrasoundneuroendocrine tumorpancreasprognostic markers

Identifiers

PMID31846235
PMCPMC7079001
OpenAlexW2995997168

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.