| Pituitary adenoma is a common tumor in brain and ocupies about 10%to 15%of intracranial tumors.In some cases,the tumor grows breakthrough the capsule and invades the dural,optic nerve,saddle bone or other adjacent structures,leading to related nerve and endocrine symptoms.This is the so called the invasive pituitary adenoma.The invasive pituitary adenoma is difficult to be completely removed by surgery and controlled by radiotherapy or chemotherapy.Thus it is easier to relapse after surgery,and seriously endangers the quality of life of patients.Previous studies have shown that the expression of matrix metalloproteinases(MMPs)MMP-2 and MMP-9 in invasive pituitary tumors was significantly increased;these MMPs degrade the ECM laminin,and therefore may play an important role in promoting the proliferation,poor differentiation,invasion and metastasis of pituitary adenoma.In recent years,it has been found that in breast cancer,esophageal squamous cell carcinoma,hepatoblastoma and glioma.the gene of the reverse transcription-rich cysteine-rich protein with kazal motifs(RECK)can inhibit the invasion and metastasis of the tummor by inhibiting MMPs.It has also been reported that HOX transcript antisense RNA(HOTAIR)can increase the invasion of tumor cells by promoting the expression of MMP-2 and MMP-9.However,whether the HOTAIR and RECK are involved in the regulation of human pituitary tumor invasion is till unknown.Therefore,the present study investigated the expression of HOTAIR,RECK and MMP-2,9 in different types of human pituitary adenomas,and analysed their relationship with the invasion and metastasis of the tumorPart I An analysis on clinical biology of human pituitary adenomas,in relation to pituitary hormone levels and tumor invasionOBJECTIVE:To investigate clinical symptoms of human pituitary adenomas in relation to the local expressionof immunohistochemical staining of pituitary tumor and the corresponding hormone levels and clinical symptoms in preoperative serum to explore its relationship with invasion.Methods:Clinical datas of 195 patients were analyzed who undwent pituitary surgery in Department of Neurosurgery of Renmin Hospital of Wuhan University from January 2013 to June 2016,including head CT and MRI,preoperative serum pituitary hormone test results;postoperative resection of histopathology HE staining and immunohistochemistry.To study the clinical manifestations of pituitary adenomas in clinical morbidity,serology and pathologic immunohistochemistry,the difference of clinical manifestations of invasive pituitary adenoma and noninvasive pituitary adenomas were statistically analyzed.Results:1.The peak ages of total pituitary adenoma were 40-60 years,with the prolactin adenoma,growth hormone adenoma and nonfunctioning adenoma as the three leading types.For different types,the age distribution was different.Prolactin adenoma was more common in patients aged 30-50 years,probably due to the age-related changes in PRL secretion;growth hormone adenoma had an peak ages at 40 and 50,and no functional adenoma is consistent with the ages of total pituitary adenomas.2,Invasive pituitary adenoma accounted for 42%of the incidence of total pituitary adenoma,in which the no functional and prolactin types were the highest(12.8%and 9.2%,respectively),probably because these types have inapparent early symptoms and are usually diagnosed in later stages.GH pituitary Adenoma had a low invasive ratio due to its early acromegaly symptoms.The patients under 20 years old had a high proportion of invasive pituitary adenoma with a higher malignant degree.3,For PRL pituitary adenoma patients diagnosed with clinical symptoms and image,pathological diagnosis of the results with the serum PRL levels of 90ng/ml and 150ng/ml as diagnostic criteria for prolactinare consistent.For serological testing Patients who do not agree with the pathological diagnosis should be diluted several times after the determination of serum to avoid missed and misdiagnosed.4,For GH tumor patient serum GH level determination for the diagnosis of GH tumor is very specific,the patient’s preoperative serum GH level determination of the diagnosis of clinical GH tumor has a guiding significance,postoperative serum GH levels can reflect the resection degree of tumor completely or not.Patients with serological test results and immunohistochemical results inconsistent need to consider the detection of mixed adenoma by monoclonal antibody results in misdiagnosed.Conclusions:Different pathologic types of pituitary adenomas were different from the peak age,which was related to the time of clinical symptoms,and the proportion of invision pituitary tumor were highestin non-functional adenomas and prolactin adenomas.Serum GH levels are well related to the pathological diagnosis of GH pituitary adenoma.Part II Expression and invasion of MMP-2,9 and RECK proteins in human pituitaryObjectives:To investigate the expression of MMP-2,MMP-9 and RECK protein in human pituitary adenomas of various pathological types,and to analyze the differences between invasive pituitary adenomas and non-invasive pituitary adenomas,and to explore themechanism and controllability in invasive growth pituitary tumors.Methods:30 human pituitary tumor specimens obtained by operation were divided into two parts,one specimen was fixed with paraformaldehyde to examine the expression of RECK,MMP-2 and MMP-9 protein in pituitary adenomas of different pathological types by immunohistochemistry.Another specimen was quickly put into liquid nitrogen cryopreservation to examine the expressions of RECK,MMP-2 and MMP-9 by western blot.The related factors of expression difference were analyzed and the possible regulation mechanism was analyzed.Results:The results of immunohistochemistry showed the expression of MMP-2 and MMP-9 in non-invasive pituitary adenomas was weakly expressed while RECK protein was positive expression;and in invisive pituitary adenomas the expression of MMP-2 and MMP-9 protein was positive or strongly positive expression,while RECK protein was weakly positive or negative expression.The results of western blot were consistent with the results of immunohistochemistry.CONCLUSION:The expression of RECK was negatively correlated with the expression of MMP-2 and MMP-9 in human pituitary adenoma.The expression of RECK protein in invasive pituitary adenoma was significantly lower than that in non-invasive pituitary adenoma.The expression of RECK protein in human pituitary adenomas may inhibit the growth of MMP-2 and MMP-9,thus inhibiting the invasive growth of pituitary adenomas.Part Ⅲ Expression of HOTAIR in Invasive Pituitary TumorsObjective:To analyze the difference of expression of HOTAIR in invasive and noninvasive pituitary adenomas,and to explore its relationship with the invasion of pituitary adenomas and the significance of molecular markers as long-term prognosis of pituitary adenomas.Methods:30 cases of human pituitary adenomas were analyzed in this study(cases are the same as the second part for western blot).The expression of HOTAIR mRNA in different pathologic types and non-invasive pituitary adenomas was detected by qRT-PCR,and the differences were discussed.Results:1.There was significant difference in the expression of HOTAIR between human invasive pituitary adenoma and noninvasive pituitary adenoma,The expression of HOTAIR in invasive pituitary adenoma was significantly higher.2.There was a significant correlation between the expression level of HOTAIR and the invasiveness of pituitary adenoma,and there was no significant correlation with the sex,age and pathological type of pituitary tumor.3.The expression of HOTAIR in human pituitary adenoma was positively correlated with the expression of MMP-2 and MMP-9.Conclusion:HOTAIR is highly expressed in human invasive pituitary adenomas and is positively correlated with the expression of MMP-2 and MMP-9,Suggesting that HOTAIR can induce up-regulation of MMP-2 and MMP-9 expression and promote invasive growth of human pituitary tumors,similar to other malignancies.HOTAIR is expected to be a molecular marker for clinical testing of invasive pituitary adenomas... |
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