Cyclin D and cyclin E expression in normal and adenomatous pituitary

Objectives: Cyclins play an important role in the regulation of cell progre ssion through the cell cycle. Over-expression of the cyclins has been shown in many different tumour types. Pituitary adenomas are a common form of en docrine neoplasia in the human, but have been little studied in terms of th e expression of the principal cyclins regulating checkpoint exit, cyclin D1 and cyclin E. Methods: We therefore investigated the expression of cyclin D1 and cyclin E in a range of benign and metastatic pituitary tumours. We studied a total of 95 pituitaries. including normal pituitary (n = 20), Gushing's disease ( n = 19), somatotroph tumours (n = 19), non-functioning adenomas (n = 18), p rolactinomas (n = 7), aggressive tumours (n = 9) and pituitary carcinoma (n = 3). All tumours and normal tissue were immunostained for cyclin D1 and c yclin E using a standard technique, and were then subjected to blinded anal ysis by a single observer and the extent of staining quantified on the basi s of 500 cell counts per tissue. The distribution of positive staining betw een different tissues was analysed by non-parametric test procedures. Results: There was no cytoplasmic staining for cyclin D1 in any tissue. Nuc lear staining was generally sparse, but was statistically more frequent in non-functioning and aggressive tumours compared with other tumour types or normal pituitary. Cyclin E was also sparsely expressed, but was specificall y increased in corticotroph tumours from patients with Gushing's disease. Conclusions: We report cyclin D1 over-expression in aggressive and non-func tioning pituitary tumours, and that cyclin E expression is more frequently seen in Gushing's disease. The high level of cyclin E expression in Gushing 's disease may relate to the low level of p27 protein expression previously reported in corticotroph tumours.