Jordan S, Lidhar K, Korbonits M, Lowe D G, Grossman A B
Department of Histopathology, St Bartholomew's Hospital, London EC1A 7BE, UK.
Eur J Endocrinol. 2000 Jul;143(1):R1-6. doi: 10.1530/eje.0.143r001.
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.
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.
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.
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.
细胞周期蛋白在调控细胞通过细胞周期进程中发挥重要作用。在许多不同类型肿瘤中均已发现细胞周期蛋白的过表达。垂体腺瘤是人类内分泌肿瘤的常见形式，但在调控关卡退出的主要细胞周期蛋白（细胞周期蛋白D1和细胞周期蛋白E）的表达方面研究较少。
因此，我们研究了细胞周期蛋白D1和细胞周期蛋白E在一系列良性和转移性垂体肿瘤中的表达。我们共研究了95个垂体，包括正常垂体（n = 20）、库欣病（n = 19）、生长激素瘤（n = 19）、无功能腺瘤（n = 18）、催乳素瘤（n = 7）、侵袭性肿瘤（n = 9）和垂体癌（n = 3）。使用标准技术对所有肿瘤和正常组织进行细胞周期蛋白D1和细胞周期蛋白E免疫染色，然后由一名观察者进行盲法分析，并根据每个组织500个细胞计数对染色程度进行量化。通过非参数检验程序分析不同组织之间阳性染色的分布情况。
在任何组织中均未发现细胞周期蛋白D1的细胞质染色。核染色通常稀疏，但与其他肿瘤类型或正常垂体相比，在无功能和侵袭性肿瘤中在统计学上更常见。细胞周期蛋白E也表达稀疏，但在库欣病患者的促肾上腺皮质激素细胞肿瘤中特异性增加。
我们报告了侵袭性和无功能垂体肿瘤中细胞周期蛋白D1的过表达，并且细胞周期蛋白E的表达在库欣病中更常见。库欣病中细胞周期蛋白E的高表达水平可能与先前报道的促肾上腺皮质激素细胞肿瘤中p27蛋白表达水平低有关。
