Expression of activin and inhibin in human endocrine tumours — ASN Events

Expression of activin and inhibin in human endocrine tumours (#259)

Francesco E Marino 1 , Gail Risbridger 2 , Elspeth Gold 1
  1. Anatomy, University of Otago, Dunedin, New Zealand
  2. Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia

The inhibin knock-out mouse showed inhibin-α was a tumour suppressor as this mouse develops testis/ovarian tumours, and when gonadectomised adrenal tumours. Tumour development leads to elevated activins which contribute to tumour progression. In contrast, clinical data reports up-regulation of inhibin-α in GCT’s, Sertoli and Leydig cell tumours and in adrenocortical adenocarcinomas. Discrepant results from mouse and human raise the following questions: Is inhibin-α a tumour suppressor in humans and does aberrant expression of inhibin, and activins contribute to human gonadal and adrenal tumours. Therefore we aimed to investigate the expression of inhibin-α, activin-βA, -βB, activin antagonists, (follistatin, activin-βC), intracellular signalling molecules (Smad-2, Smad-3) and activin receptors (ActRIIA, ActRIIB) in human testicular, ovarian and adrenal tumours compared to normal controls. Cancer tissue arrays with normal controls (US Biomax) were used to assess inhibin-α, activin-βA, -βB, -βC, follistatin, ActRIIA and ActRIIB staining. Tissue cores were given a score according to the intensity and the extent of staining. An immunoreactive score was determined by multiplying intensity and extent, with a minimum score of 0 and a maximum score of 12. Nuclear localisation of Smad-2 and Smad-3 in tissue cores were estimated based on a method that allowed an unbiased semi-quantitation of the percentage of positive cells. Data were analysed using Mann-Whitney U Test (SPSS), significant values to date are displayed in Table 1. Like the inhibin knock-out mouse, increased activin-βA was evident in tumours examined to date. Assessment of other subunits and signaling molecules will determine their contribution to gonadal and adrenal tumours.

Table 1: Fold difference in activin immunoreactive score vs normal control.







Germ Cell Seminoma

 (n =48)







Non-Germ Cell Seminoma

(n = 19)



Sex-Cord Stromal

(n = 30)



Germ Cell

(n = 35)