| Background and ObjectivesPituitary adenoma is a benign intracranial adenoma in histology. However, according to biological behavior it can be divided into two types of growth, invasive and expansive. Invasive pituitary adenoma is a kind of pituitary tumor that grows towards normal skull, dura, cavernous sinus, sphenoid sinus, suprasellar, parasellar., which also invades and damages its surrounding brain tissue, dura mater and bones. Clinic found that the majority of invasive pituitary adenoma are non-functioning or prolactin adenoma, a small number the growth hormone adenoma. It has low total removal rate, and high recurrence rate. Currently, it is difficult for histopathological features alone to objectively evaluate the invasive biological behavior of pituitary adenomas, with little development in total cure. Human telomerase reverse transcriptase (hTERT) of human telomerase catalytic subunit protein, is rate-limiting component of telomerase, in the regulation of telomerase activity may play an important role in telomerase activity in malignant tumors closely related with the level of hTERT mRNA. Therefore. hTERT expression in telomerase activation and carcinogenesis is the rate-limiting step; may induce a variety of tumor cell differentiation, and promote the malignant value-added, could inhibit tumor cell apoptosis. Peroxidase value-added activated receptor (PPAR-y) is a member of the nuclear receptor superfamily, one of which can regulate cell differentiation, metabolism and insulin sensitivity, the dysfunction of their receptors will lead to the body to produce series of diseases。The signal transduction pathways plays a role in the function of hTERT and PPAR-γ, but whether they have synergy between them in the tumor s growth and development is still unknown。Up to now, no report on the expression of telomerase reverse transcriptase in the pituitary, reports on such also less, and the reports on hTERT and PPAR-γalso have not been reported at home and abroad.Now hTERT, PPAR-y is thought to function gteatly in tumor growth, differentiation and invasion. We use PCR to detect and explore the effects that hTERT and PPAR-γs expression in invasive pituitary adenomas and development and the value to be a marker to predict biological behaviours, and further to predict the relevant role in prognosis and treatment of pituitary adenomas.Materials and MethodsThe 42 Specimens were taken from Neurosurgery diagnosis of clinical and surgical resection of the First,Second Affiliated Hospital of Zhengzhou University from 2009 to 2010, and proved by pathology, male 22 and female 20, age of 17 to 63 years, average age 45.6 years. Endocrine examines:9 nonfunctional cases,6 growth hormone adenoma cases, and 27 prolactin adenomas cases. In this study, all samples were first discovered, did not receive radiation or chemotherapy, are large adenomas (diameter> lcm) MR scanned, have complete clinical data and all were graded staged and grouped on the basis of the Wilson-improved hardy standard classification system: Invasive pituitary adenoma 18 cases, non-invasive group 24 cases. The criteria of determining invasion:①Hardy-Knosp grading and staging, III level or above and C-E;②sellar dura and adjacent bone are confirmed to have tumor cells;③imaging the tumor surrounding the internal carotid artery. Those that meet any of the above three are classified as aggressive. TRAP-PCR silver staining is used to examine the expression of telomerase (hTERT) gene in 42 cases of mRNA of pituitary adenoma, but also by RT-PCR, examine the expression situation of PPAR-y gene in 42 cases of mRNA of pituitary adenoma. Statistics by SPSS 16.0 statistical software, testing standard a=0.05.Results 1. TRAP-PCR test results:In 42 cases of pituitary adenoma, hTERT appears positive in 4 cases,38 cases had negative expression, the total positive rate is 9.5%. In the invasive group, hTERT appears positive in 4 cases of expression, negative expression occurred in 14 cases, the positive rate is 22.2%; in non-invasive group, hTERT appears negative in 24 cases. Invasion group and non-invasive group in the positive rate of hTERT expression have significant statistical difference (p=0.03l,p< 0.05); There were significant differences between the 4 cases of invasive pituitary adenom which the hTERT expression was positive and 24 cases of non-invasive pituitary adenomas which the hTERT expression was negative(t= 10.738, p= 0.000), while there was no significant difference between the 14 cases of invasive pituitary adenoma which the hTERT expression was negative and 24 cases of non-invasive pituitary adenomas (t=-0.254, p= 0.802).2. RT-PCR test results:In 42 cases of pituitary adenoma, PPAR-y positive expression in 22 cases,20 cases of negative expression, the total positive rate is 52.4%. In the invasive group, PPAR-y positive expression in 13 cases,5 cases of negative expression, the positive rate is 72.2%; PPAR-y positive expression in 9 cases, 15 cases of negative expression, the positive rate is 37.5%. Invasion group and non-invasive group in the PPAR-y positive expression rate was significantly different (p<0.05). Invasive pituitary adenoma PPAR-y expression levels is 0.972±0.103, non-invasive pituitary adenomas PPAR-y expression levels is 0.121±0.013, both had significant statistical difference (t=163.61,p<0.05). In the non-functioning adenomas, between the invasive group (0.937±0.091) and non-invasive group (0.189±0.016), the PPAR-γgene expression were significantly different (t=88.54.p<0.05); while in growth hormone adenomas, between the invasive group (0.413±0.055) and non-invasive group (0.307±0.032), the levels of PPAR-y gene expression was no significant difference (t=2.45,p> 0.1);In prolactin adenoma, between invasive group (0.930±0.087) and non-invasive group (0.064±0.011) the PPAR-γgene expression was significantly different (t= 20.56,p<0.05).3. Correlation Analysis:in the invasive pituitary adenomas samples with high mRNA expression of hTERT genes, PPAR-y expression tended to increase, the two showed correlation statistically,Spearman correlation coefficient was 0.309* (p <0.05).Conclusions1. hTERT expresses positive in invasive pituitary adenomas; PPAR-γexpression increased in the pituitary adenoma, and with the increased invasiveness of pituitary adenomas, PPAR-y expression activity was enhanced.2.hTERT and PPAR-γexpressions in invasive pituitary adenomas were positively correlated. PPAR-y amount expression and hTERT stronger activity expression are not isolated incidents.3. Between the invasive pituitary adenomas and non-invasive adenomas, there exists significant difference about the expression of PPAR-y in the non-functional type, but no significant difference in the type of growth hormone, the results need to further study. |
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