E. Papadimitriou*a (Dr), G. Kyriakopoulosb (Dr), K. Barkasc (Dr), I. Gkalonakisc (Mr), P. Pantoulac (Mrs), G. Kaltsasa (Prof), S. Theocharisd (Prof), Kι. Alexandrakid (Dr)

a LAIKO UNIVERSITY HOSPITAL, National and Kapodistrian University of Athens, Athens, GREECE ; b EVAGELISMOS GENERAL HOSPITAL, Athens, GREECE ; c NIKAIA GENERAL HOSPITAL, Athens, GREECE ; d Medical School, National and Kapodistrian University of Athens, Athens, GREECE

* eirini.d.papadimitriou@gmail.com

Introduction:Ephrin receptors (EPHs) compose the largest known subfamily of receptors tyrosine kinases and are bound and interact with EPHs-interacting proteins (Ephrins).Aim of the study was to investigate their expression in pituitary adenomas and their correlation with somatostatin receptor (SSTRs) expression.Methods:We studied 18 patients (9 males; median age 54; females median age 59) with pituitary adenomas (7 somatotropic, 2 corticotropic, 8 non-functioning (NFPAs) adenomas , 1 prolactinoma).Immunohistochemical expression of EPH-A4,-A5,-B2,-B5, SSTR2a, SSTR5, Ε-cadherin were evaluated. Positivity for EPHs is defined with a >4% of pituitary cells positive staining.An immunoreactive score (IRS) is defined by the sum of percentage of EPHs positivity (0/negative staining:0-4%; 1:5-30%; 2:31-60%; 3:61-100%); intensity of staining (0:negative staining, 1:mild; 2:intermediate; 3:intense).Low, medium or high EPH expression was defined if the total score was 0-2, 3-4, 5-6, respectively.The H-score was determined by adding the results of multiplication of the percentage of cells with staining intensity ordinal value (scored from 0 to 3).SSTRs expression was determined according Volante score.Results:Cytoplasmic and nuclear pattern of immunohistostaining was noted for EPH-A4 and cytoplasmic for EPH-A5,-B2, -B4. Positivity for EPH-A4 was seen in 17/18(94%) of the specimens(17/18 cytoplasmic; 13/18 nuclear pattern).All corticotropic and somatotropic adenomas were positive for EPH-A4. EPH-A4 IRS was mild for 4, intermediate for 6, intense for 3 cases.Only H-score for EPH-A4 expression was high ranging from 30-255.Expression of SSTR2a was noted in 6/13 (46%) and of SSTR5 in 4/8 (50%) of specimens.The corticotropic and 80% of somatotropic adenomas (4/5), which expressed SSTR2a showed intermediate and intense staining for EPHA4 with both patterns.All somatotropic (2/2) and corticotropic (2/2) adenomas expressed SSTR5, also expressed EPHA4 with both patterns.None of the NFPAs expressed SSTR2a(5/5) or SSTR5 (4/4) as opposed to EPHA4, which was expressed by 87.5% of NFPA (7/8). Sixty-six percent (2/3) of NFPA, which expressed EPH-A4 expressed also Ε-cadherin.Conclusion:Our data indicate for the first time the increased expression of mainly EPH-A4 in pituitary adenomas.The pattern of co-expression of EPH-A4 with SSTR was seen only in functional pituitary adenomas.

The author has declared no conflict of interest.