Evidence map›Paper›PMID 39425842›Full record

SynthesisEndocrine2025

Immunohistochemical expression of ephrin receptors in neuroendocrine neoplasms: a case-series of gastroenteropancreatic neuroendocrine neoplasms and a systematic review of the literature.

Krystallenia I Alexandraki, Eirini Papadimitriou, Ariadni Spyroglou, Angeliki Karapanagioti, Ioanna Antonopoulou, Irini Theohari, Odysseas Violetis, Georgios C Sotiropoulos, Stamatios Theocharis, Gregory A Kaltsas

Abstract readSystematic Review
PubMed Publisher
In one paragraph

Synthesis in Endocrine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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

10 authors.

Krystallenia I Alexandraki *Second Department of Surgery, Aretaieio Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. alexandrakik@gmail.com.
Eirini Papadimitriou *Endocrine Unit, First Department of Propaedeutic Medicine, Laiko University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Ariadni SpyroglouSecond Department of Surgery, Aretaieio Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Angeliki KarapanagiotiEndocrine Unit, First Department of Propaedeutic Medicine, Laiko University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Ioanna AntonopoulouEndocrine Unit, First Department of Propaedeutic Medicine, Laiko University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Irini TheohariFirst Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Odysseas VioletisSecond Department of Surgery, Aretaieio Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Georgios C SotiropoulosSecond Department of Propaedeutic Surgery, National and Kapodistrian University of Athens, Athens, Greece.
Stamatios Theocharis *First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Gregory A Kaltsas *Endocrine Unit, First Department of Propaedeutic Medicine, Laiko University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeErythropoietin-producing hepatocellular (EPH) receptors are the largest known family of tyrosine kinases receptors (TKR) in humans, implicated in cell proliferation, adhesion, migration, tumor angiogenesis, invasion and metastasis. The aim of the present study is to assess the expression of EPHs in neuroendocrine neoplasms (NENs).

methodsImmunohistochemical staining of specimens of 30 patients with gastroenteropancreatic and lung NENs was performed for EPH-A1, EPH-A2, EPH-A4, EPH-A5 protein expression, in addition to ki-67 multiplication index and programmed death-ligand 1. Additionally, we performed a systematic review of the available literature in three different databases reporting on the expression of EPH in all neuroendocrine neoplasms.

resultsPositive expression was seen in 16/19 (84%) specimens for EPH-A1, 15/23 (65%) for EPH-A2, 21/24 (88%) for EPH-A4, 24/26 (92%) for EPH-A5. EPH-A1 was expressed in 9/9 pancreatic, 3/4 small intestine, but not in one lung NEN, EPH-A2 in 5/10 pancreatic, 3/4 small intestine and lung, and in one of each of gastric, appendix, colorectal, and cervical NENs, respectively. EPH-A4 showed positive expression in 9/11 pancreatic, 4/4 small intestine, 3/3 lung specimens and EPH-A5 in 10/11, 4/4 and 4/4, respectively. Data retrieved from the systematic review of the literature in combination with the data from the present study are suggestive of a frequent EPH expression in pituitary, thyroid, lung and gastroenteropancreatic NENs, yet, with varying expressions of the single receptor subtypes.

conclusionEPHs may have a role in NEN tumorigenesis, prognosis as well as a role in the evolving molecular-targeted therapies.

Indexed as

Gastrointestinal NeoplasmsIntestinal NeoplasmsLung NeoplasmsNeuroendocrine TumorsPancreatic NeoplasmsReceptors, Eph FamilyStomach NeoplasmsAdultAgedFemaleHumansImmunohistochemistryMaleMiddle AgedReceptors, Eph FamilyEPH-A1EPH-A2EPH-A4EPH-A5Ephrin receptorNeuroendocrine tumorsPD-L1

Identifiers

PMID39425842

What OpenQuestion holds

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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.