ECE2019 Poster Presentations Adrenal and Neuroendocrine Tumours 3 (70 abstracts)
Immunohistochemical expression of ephrines A2 and A4 receptors in neuroendocrine neoplasms: preliminary results
Krystallenia Alexandraki 1 , Ioanna Antonopoulou 1 , Maria Karaflou 1 , Charikleia Christakou 1 , Vasiliki Mavroeidi 1 , Aggeliki Karapanagioti 1 , Maria Lekkakou 1 , Elli Anagnostou 1 , Marina Tsoli 1 , Anna Angelousi 1 , Ioanna Kassiani Delladetsima 2 , Evangelos Felekouras 3 , Georgios Sotiropoulos 4 , Gregory Kaltsas 1 & Stamatios Theocharis 2
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.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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