Endocrine Abstracts

Pituitary adenomas are benign tumours, which do not involve mutations in tumour suppressor genes or oncogenes. We have shown that the canonical Raf/MAPK and PI(3)K/Akt pathways are over-activated in these tumours, but their downstream effectors are modified to a much lesser extent. It is probable that the oncogenic mutations responsible for the initiation of these tumours therefore lies proximal to the convergence of these pathways, at or even upstream to the growth factor receptor(s). However, the ability of these tumours to grow extremely slowly or, in many cases, to stop growth entirely has been difficult to understand. Oncogene-induced senescence (OIS) is a process whereby tumours can undergo growth cessation or attenuation in the presence of oncogenic mutations or over-expression. We have speculated that such OIS also occurs in pituitary adenomas, and that loss of this mechanism may account for the very rare prevalence (~0.2%) of carcinomatous change in pituitary tumours. We therefore have compared the expression of β-galactosidase, as a marker of OIS, in pituitary adenomas and normal pituitary tissue using quantitative immunohistochemistry.

Pituitary adenomas (n=42) and normal pituitary (n=7) were stained for β-galactosidase immunostaining and scored semi-quantitatively in a blinded manner. Senescence-associated β-galactosidase expression was significantly increased in GH-secreting and NFPAs compared to normal pituitary, but its expression in prolactin- and ACTH-secreting tumours was similar to the normal tissue. All staining was cytoplasmic, and was absent when non-specific anti-serum was used as a control.

We conclude that two major sub-groups of pituitary tumours showed over-expression of β-galactosidase, suggestive of OIS, although this was not seen in the two subgroups, prolactin- and ACTH-secreting, which are most likely to undergo malignant transformation. We are currently exploring the expression of β-galactosidase in pituitary carcinomas. It seems probable that OIS plays a significant role in maintaining the benign nature of most pituitary adenomas.