Endocrine Abstracts

Introduction: Ephrin receptors (EPHs) compose the largest known subfamily of receptors tyrosine kinases and are bound and interact with EPHs-interacting proteins (Ephrins). They have a role in tumor growth, invasion, angiogenesis and metastasis of several neoplasms. Aim of the study was to investigate the expression of EPH-A4, -A5, -B2 and -B5 in pituitary lesions.

Material and Methods: Our study group consisted of 18 patients (9 males with median age 54 and females with median age 59) with pituitary lesions (7 somatotropic and 2 corticotropic adenomas, 8 non-functioning macro-adenomas and 1 resistant prolactionoma). Formalin fixed-paraffin embedded (FFPE) tissue sections from the lesions were assessed immunohistochemically for EPH-A4, -A5, -B2 and -B5 expression. Positivity is defined when >4% of pituitary cells have positive staining, after observation of at least 1000 cells. An immunoreactive score (IRS) was created according to the sum of percentage of EPH-A4, -A5, -B2 and -B5 positivity (0/negative staining: 0–4% of pituitary cells positive; 1: 5–30% of pituitary cells positive; 2: 31-60% of pituitary cells positive; 3: 61–100% of pituitary 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 low, medium or high EPH expression if the total score was 0-2, 3-4 and 5-6, respectively. The H-score is determined by adding the results of multiplication of the percentage of cells with staining intensity ordinal value (scored from 0 for “no signal” to 3 for “strong signal”) with 300 possible values.

Results: Cytoplasmic and nuclear for EPH-A4 and cytoplasmic for EPH-A5, -B2 and -B4 pattern of immunostaining was noted. Positivity for EPH-A4 was seen in 17/18 (94%) of the specimens (17/18 with cytoplasmic and 13/18 with nuclear pattern). All corticotropic and somatotropic adenomas found positive for EPH-A4 with both patterns. Positivity for EPH-A5 and EPH-β2 was seen in 4/18 (22%) specimens and for EPH-β4 in 1/18 (5.5%), all non-functioning adenomas with cytoplasmic pattern. EPH-A4 IRS was mild for 4, intermediate for 6 and intense for 3 cases. H-score for EPH-A4 expression ranging from 30-255, whereas for EPH-A5,-B2 and -B4 was lower (10-65).

Conclusion: Our data indicate for the first time the increased expression of mainly EPH-A4 and to a lesser extent of EPH-A5, -B2 and -B4 in pituitary lesions. Their involvement in the pathophysiology of pituitary lesions requires further investigation to clarify their role and their possible potential prognostic value.