Granulosa theca cell tumor in an Arabian mare: Are immunohistochemically loss of GDF-9 and BMP-6 proteins associated with high GATA-4, inhibin-?, AMH expressions?

Abstract

Bir Arap kısrağında granuloza-teka hücre tümörü (GTHT); klinik, patomorfolojik ve immunohistokimyasal (İHK) incelemelerle teşhis edildi. İmmunohistokimyasal olarak GTHT’de; Transforming Growth factor-? ailesi [GDF-9 Growth Diff erentiation Factor-9 (GDF-9), Bone Morphogenetic Protein-6 (BMP-6), anti-Müllerian Hormone (AMH) ve inhibin-?], GATA ailesi (GATA-4 ve GATA-6) ve Insulin-like Growth Factor ailesi (IGF-1 and IGF-2) üyelerinin olası rolleri ortaya konmaya çalışıldı ve bulgular iki negatif kontrol ovaryum dokusuyla karşılaştırıldı. Neoplastik ovaryum dokusunda AMH, inhibin-?, IGF-2, GATA-4 orta derecede, IGF-1, GATA-6 ise hafif derecede pozitif sonuç verirken GDF-9 ve BMP-6 pozitifl ik göstermedi. Ayrıca kontrol grubu dokuların boyamalarında tüm belirteçler ile orta derecede pozitif sonuçlar elde edildi. Kısraklarda GTHT tümörogenezisinde yüksek GATA-4, AMH ve İnhibin-? düzeylerinin, GDF-9 ve BMP-6 eksikliğindeki önemli rolünü belirlemede mitojenik ve stres sinyallerine yanıttaki genlerin aktivasyonundan sorumlu transkripsiyon faktörlerinin de yeni moleküler çalışmalar ile incelenmesi gerekliliğini ortaya koymuştur.

Granulosa-theca cell tumor (GTCT) in an Arabian mare was diagnosed by clinical, pathomorphological and immunohistochemical (IHC) examinations. Immunohistochemically, it was tried to clarify the possible roles of Transforming Growth Factor–β superfamily members [Growth Diff erentiation Factor-9 (GDF-9), Bone Morphogenetic Protein-6 (BMP-6), anti-Müllerian Hormone (AMH) and inhibin-α], GATA family members (GATA-4 and GATA-6) and Insulin-like Growth Factor family (IGF-1 and IGF-2) on GTCT and results was compared with two negative control ovarian tissues. Moderate positivities with AMH, inhibin-α, IGF-2, GATA-4, and mild positivities with IGF-1, GATA-6 were obtained whereas no positivity could be shown with GDF-9 and BMP-6 in neoplastic ovarian tissue. Additionally, mild positivities were obtained with all markers in control stainings. Further molecular studies for transcription factors regulating activation of genes in response to mitogenic and stress signals in equine GTCT tumorigenesis are needed to elucidate whether the high GATA-4, AMH, and inhibin-α immunopositivities play a significant role on GDF-9 and BMP-6 deficiency.