Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, P.R China.
Anticancer Res. 2013 Aug;33(8):3123-31.
Pituitary ademonas are benign tumours with different biological behaviour, especially with regard to tumour size, invasion, endocrine function, intratumour cystic lesion and apoplexy. There is little understanding of the growth and the control of progression of pituitary tumours. In the present study, we investigated the expression of mammalian target of rapamycin (mTOR) pathway regulators, in clinical pituitary adenomas. Pituitary adenomas from 95 patients were included in the study. Fresh pituitary tumours were obtained immediately after surgery and processed for histological, immunohistological and molecular based analyses. Histolopathological and clinical information including tumour stage, invasion characteristic and endocrine status were analysed against the gene transcript expression of mTOR, RAPTOR and RICTOR. There was a stepwise and significantly increased relation-ship between RICTOR expression and tumour size, namely p=0.0012 and p=0.0055 for tumours 1-2 cm and tumours >3 cm compared with tumours <1 cm respectively. Significantly higher levels of mTOR were seen in tumours with cystic lesions (p=0.044). There was no significant correlation between mTOR, RAPTOR and RICTOR and tumour apoplexy, nor a correlation between mTOR, RAPTOR and RICTOR with suprasephanous spread and sella floor destruction. However, pituitary tumours with cavernous sinus invasion, namely Knosp stage 3-4 had significantly lower levels of RAPTOR than those of Knosp stage 1-2 (p=0.01). A similar but statistically insignificant trend was seen with RICTOR. Using modified Hardy's staging, it was found that there was a significant correlation between tumour stage and RAPTOR and RICTOR expression. mTOR and RAPTOR levels differed in tumours with different endocrine functions, although no statistical difference was observed. However, Growth Hormone (GH) -, Follicle-Stimulating Hormone (FSH)-, Thyroid Stimulating Hormone (TSH)-secreting tumours had significantly lower levels of RICTOR compared with nonfunctional tumours. Finally, levels of mTOR were found to be significantly correlated with levels of both RAPTOR and RICTOR. It is noteworthy that RAPTOR and RICTOR levels were also significantly correlated. In conclusion, mTOR pathway regulators, mTOR, RAPTOR and RICTOR are significantly correlated with the invasion, staging, and tumour growth of pituitary adenomas and thus have an important predictive and prognostic value in patients with pituitary adenoma.
垂体腺瘤是具有不同生物学行为的良性肿瘤，特别是在肿瘤大小、侵袭性、内分泌功能、肿瘤内囊性病变和卒中方面。目前对垂体瘤的生长和进展控制了解甚少。本研究旨在探讨哺乳动物雷帕霉素靶蛋白（mTOR）通路调节剂在临床垂体腺瘤中的表达。研究纳入了 95 例垂体腺瘤患者。术后立即获取新鲜垂体肿瘤，进行组织学、免疫组织化学和分子分析。分析 mTOR、RAPTOR 和 RICTOR 的基因转录表达与肿瘤分期、侵袭特征和内分泌状态之间的关系。RICTOR 表达与肿瘤大小呈逐步显著正相关，即 1-2cm 肿瘤与 3cm 以上肿瘤相比，p=0.0012 和 p=0.0055；而 1cm 以下肿瘤，p=0.0012 和 p=0.0055。有囊性病变的肿瘤中 mTOR 水平显著升高（p=0.044）。mTOR、RAPTOR 和 RICTOR 与肿瘤卒中无显著相关性，mTOR、RAPTOR 和 RICTOR 与鞍上扩展和鞍底破坏亦无相关性。然而，海绵窦侵袭的垂体腺瘤，即 Knosp 3-4 期，RAPTOR 水平明显低于 Knosp 1-2 期（p=0.01），而 RICTOR 则有类似但统计学上不显著的趋势。使用改良 Hardy 分期，发现肿瘤分期与 RAPTOR 和 RICTOR 表达之间存在显著相关性。不同内分泌功能的肿瘤 mTOR 和 RAPTOR 水平不同，但无统计学差异。然而，生长激素（GH）-、促卵泡激素（FSH）-、促甲状腺激素（TSH）-分泌肿瘤的 RICTOR 水平明显低于无功能肿瘤。最后，mTOR 水平与 RAPTOR 和 RICTOR 水平显著相关。值得注意的是，RAPTOR 和 RICTOR 水平也显著相关。总之，mTOR 通路调节剂 mTOR、RAPTOR 和 RICTOR 与垂体腺瘤的侵袭、分期和肿瘤生长显著相关，因此对垂体腺瘤患者具有重要的预测和预后价值。
