Cyclin D and cyclin E expression in normal and adenomatous pituitary

Objectives: Cyclins play an important role in the regulation of cell progression through the cell cycle. Over-expression of the cyclins has been shown in many different tumour types. Pituitary adenomas are a common form of endocrine neoplasia in the human, but have been little studied in terms of the 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), Cushing's disease (n = 19), somatotroph tumours (n = 19), non-functioning adenomas (n = 18), prolactinomas (n = 7), aggressive tumours (n = 9) and pituitary carcinoma (n = 3). All tumours and normal tissue were immunostained for cyclin D1 and cyclin E using a standard technique, and were then subjected to blinded analysis by a single observer and the extent of staining quantified on the basis of 500 cell counts per tissue. The distribution of positive staining between different tissues was analysed by non-parametric test procedures. Results: There was no cytoplasmic staining for cyclin D1 in any tissue. Nuclear 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 specifically increased in corticotroph tumours from patients with Cushing's disease. Conclusions: We report cyclin D1 over-expression in aggressive and non-functioning pituitary tumours, and that cyclin E expression is more frequently seen in Cushing's disease. The high level of cyclin E expression in Cushing's disease may relate to the low level of p27 protein expression previously reported in corticotroph tumours.