Study On Correlation Between Osteopontin,Matrix Metalloproteinase-9,Microvessel Density And Pituitary Adenomas Invasiveness

Objective:Pituitary adenoma is one of the most common intracal tumor in clinical works. They have been reported to represent 10%-15% of the whole intracal tumors.The incidence rate of pituitary adenomas is less than that of glioma and meningeoma. Pituitary adenomas often grow limitedly, but part of the tumor appearing aggressive behavior, is so called invasive pituitary adenomas. Invasive pituitary adenomas invade into the local dura blood vessels, nerve, cavernous sinus, saddle area and so on. Radical surgical treatment of the invasive pituitary adenommas is more difficult than those of non-invasives.The invasiveness of pitu- itary adenomas lead to high tumor residuc and recurrency rate. The prognosis of invasive pituitary adenommas is very bad. Now the invasiveness is the hot topic and nodus on pituitary adenomas.At present we principally depend on the clinical symptom of patient, the examination of imageology—if the tumor destroy basion, invade cavernous sinus, circumvolutio internal carotid arteria and compress optic nerve etc or not, the observation in operation—if the tumor invade dura, bone, cranial nerve and internal carotid arteria etc or not, and the biopsy dura or bone of saddle area in operation to judge the invasiveness of pituitary adenomas. But it is still limitedly on above-mentioned approach, especially in the nonage of pituitary adenomas or the minor tumor-soma of invasive pituitary adenomas. Depending on above- mentioned standard, it is hard to obtain a right diagnose and cannot take a active effectual combined therapy.Osteopontin(OPN) is a secreted phosphate-protein. Its'receptor including integrin and CD44. Generous study shows that OPN is related to many tumors on volume, growth, invasion, metastasis and even the tumor prognosis. Matrix metallo- proteinase-9(MMP-9) is the most molecular weight and the most important enzyme in the family of metalloproteinase, his substrate is collagen IV, V, VII, X. MMP-9 are proteolytic enzymes that have a capability of breaking down the extracellular matrix(ECM) and basal membrane, accordingly to promote infiltrate and transfusion. MMP-9 may play a important role in growth and invasion of intracranial tumors. MMP-9 still have specificity to judge pituitary adenomas invasiveness Tumorous growth depend on vasoformation.Microvessel density (MVD) counts is known as a index which can reflect tumor vasoformation. Microvessel density also is a significant Index which can reflect tumorous biological behaviour. Microvessel density is related to growth, recidivation and prognosis of tumor. Heighten of MVD often hint a bad prognosis to tumor patients.The aim of this study is to detect expression and correlation of OPN,MMP-9 and MVD in pituitary adenomas and to initially evaluate the relationship among them and invasiveness of pituitary adenomas. It may provided a new potential path for clinic treatment and prognosis.Materials and Methods: Tumor Samples of pituitary adenomas and normal brain tissues were obtained from 30 patients who had undergone neurosurgery from October 2006 to August 2007 at the Second Affiliated Hospital, HeBei Medical University. we also collected 3 cases normal brain tissues of decompression procedure of cerebral trauma. Nineteen patients were female and eleven were male, with the age range 17~69 years and amean age of 42 years. According to examination of imageology and observation in operation whether tumor tissues invade into the vicinity construction. Thirty examples of pituitary adenomas could divide into invasive group 17 cases and non-invasive group 13 cases.The expression of OPN,MMP-9 and MVD were differently detected by immunohistochemical S-P method in 30 cases of pituitary adenomas and 3 cases normal brain tissue. The method include specimen fixation, embedding paraffin, specimen sections, deparaffinizing and rehydrating, restoring antigen, adding the first antibody, adding the second antibody, anhydrating, making transparence, mounting, testing under microscope.The experiment datas were expressed in mean±standard deviation. Statistical analysis was performed by SPSS13.0 statistical software.OPN and MMP-9 used chi-square test. MVD used Independent-samples T test. Spearman correlation analysis was applied to correlativity between OPN and MMP-9. The associativity between OPN and MVD,MMP-9 and MVD used linear correlation analysis, moreover used T test to detect significance of correlation. The size of test wasα=0.05.Result: The expression of OPN was negative in normal brain tissue. But the most expression of OPN located in tumor cell cytoplasm.The expressions existed in non-invasive and invasive pituitary adenoma. And the expression of OPN in invasive pituitary adenoma was higher than that in non-invasive pituitary adenoma (χ2=6.652, P<0.01). The expression of OPN was negative in normal brain tissue. But the most expression of MMP-9 located in tumor cell periplast. The expression of MMP-9 in invasive pituitary adenoma was higher than that in non-invasive pituitary adenoma (χ2=8.167, P<0.01). The posi- tive staining most of FactorⅧantibody located in tumor vascular endothelial cell. Microvessel density counts in invasive pituitary adenoma was higher than that in non-invasive pituitary adenoma (t=3.581, P<0.01).There was an associativity between OPN and MMP-9 in invasive pituitary adenoma (rs =0.813, p<0.01). The expression of OPN and MVD counts in invasive pituitary adenoma were correlative (r =0.716, p<0.01). There was also an associativity between MMP-9 and MVD counts in invasive pituitary adenoma (r =0.783, p<0.01).Conclusion:The group of invasive pituitary adenoma and non-invasive pituitary adenoma have no significant deviation on sex and average years of age:p>0.05.1 Compared with non-invasive pituitary adenoma,the expr- ession of OPN and MMP-9 in invasive pituitary adenoma is enhanced expression, and is correlative. This condistion can illustrate that OPN and MMP-9 all participate the invasiveness of pituitary adenoma, and can generate synergistic effect.2 MVD counts in invasive pituitary adenoma is higher than that in non-invasive pituitary adenoma.The expression of MVD in invasive pituitary adenoma hints that tumor invasiveness is correlated to angiogenesis.There is positive correlation between the expression of OPN,MMP-9 and MVD in invasive pituitary adenoma. This positive correlation indicates that OPN,MMP-9 and MVD may all involve in tumor angiogenesis to facilitate tumor growth and invasion.3 OPN,MMP-9 and MVD are correlated to pituitary aden- omas invasiveness, which indicate that OPN,MMP-9 and MVD can evaluate invasiveness and prognostic of pituitary adenomas. Through detected to OPN,MMP-9 and MVD in the samples of pituitary adenomas, we can judge the potential invasiveness in pristine pituitary adenomas, and institute a right treatment plan to improve curative effect of tumor patients.