title: Expression of the mTOR pathway regulators in human pituitary adenomas indicates the clinical course.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, P.R China. jwttyy@sina.com
authors.forename: Wang
authors.initials: W
authors.lastname: Jia
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sanders
authors.forename: Guijun
authors.initials: G
authors.lastname: Jia
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.forename: Runchun
authors.initials: R
authors.lastname: Lu
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002426:Cavernous Sinus / Q000473:pathology; D018450:Disease Progression; D004703:Endocrine System / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology*; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D000076223:Regulatory-Associated Protein of mTOR; D015398:Signal Transduction / Q000235:genetics*; D018709:Statistics, Nonparametric; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C492571:RICTOR protein, human; C463659:RPTOR protein, human; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D000076223:Regulatory-Associated Protein of mTOR; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: Pituitary adenoma; RAPTOR; RICTOR; invasion; mTOR; staging