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Endocrine Abstracts (2019) 63 P873 | DOI: 10.1530/endoabs.63.P873

1Endocrine Unit, 1st Department of Propaedeutic Medicine, Laiko University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece; 2First Department of Pathology, Medical School, National and Kapodistrian University of At, Athens, Greece; 31st Surgical Department, Athens University School of Medicine,‘Laiko’ General Hospital, Athens, Greece; 4Second Department of Propaedeutic Surgery, National and Kapodistrian University of Athens, Athens, Greece.


Introduction: Ephrin receptors (EPHs) have a role in tumor growth, invasion, angiogenesis and metastasis of several neoplasms. Aim of the study was to investigate the expression and possible clinical significance of EPH-A4 and EPH-A2 protein expression in the pathophysiology of neuroendocrine neoplasms (NENs).

Methods: EPH-A4 and -A2 protein expression was assessed by immunohistochemical analysis along with Ki-67 proliferation index (%) on 28 paraffin embedded NENs tissue sections obtained from equal number of patients. Tumor cells’ EPH-A4 and -A2 immunoreactivity was scored according to the sum of percentage of EPH-A4 and -A2 positivity (0/negative staining: 0–4% of tumor cells positive; 1: 5–24% of tumor cells positive; 2: 25–49% of tumor cells positive; 3: 50–100% of tumor cells positive), and the intensity of staining (0: negative staining, 1: mild staining; 2: intermediate staining; 3: intense staining). A case was characterized to present either low or high EPH expression if the total score was <2 and ≥3, respectively.

Results: We studied 28 specimens from patients (16 males; median age 57, range: 26-83 years) with NENs: 12 pancreatic, 4 small-bowel, 4 lung, 2 gastric, 2 appendix, 1 colorectal, 1 gallbladder, 1 uterine, 1 unknown primary origin (UPO). Five specimens were taken from a metastatic focus and 23 from the primary tumor, 10 from Grade 1, and 9 each from Grade 2 and 3 NENs. Positivity for EPHA-2 was seen in 15/23 (65%) of the specimens (all with cytoplasmatic pattern) and in 21/24 (88%) for EPHA-4 (14% with cytoplasmatic, 53% with nuclear and 33% with both types of IHC pattern). In specimens taken from metastatic foci EPHA-4 was positive in all specimens and in 84% of tissues taken by primary tumors; similarly EPH-A2 was positive in 80% of specimens from metastases and in 61% of tissues taken by primary tumors. EPHA-4 was expressed in 9/11 (82%) pancreatic, in 4/4 (100%) small-bowel, in 3/3 (100%) lung, 2/2 (100%) gastric, 1/2 (50%) appendiceal, one (100%) colorectal, one (100%) gallbladder NENs assessed; EPHA-2 was expressed in 5/10 (50%) pancreatic, in 3/4 (75%) small-bowel, in 3/4 (75%) lung, one (100%) gastric, one (100%) appendiceal, one (100%) colorectal, one (100%) uterine NENs assessed, but it was not expressed in the UPO NEN.

Conclusions: Our preliminary data indicate a higher prevalence of EPHA-4 expression compared to EPH-A2 in NENs. The possible role of EPHs in NEN pathophysiology needs further investigation to shed light to their exact role in NENs.

Volume 63

21st European Congress of Endocrinology

Lyon, France
18 May 2019 - 21 May 2019

European Society of Endocrinology 

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