Theexpression And Correlation Of COX-2, VEGF, MMP-9 In Invasive Pituitary Adenomas

ObjectiveTo study the expression of cyciooxygense-2 (COX-2),Matrix Metallo Proteinase-9 (MMP-9)and vascular en-dothelial growth factor(VEGF) in pituitary adenomas,and analysis the relationship with the invasion of pituitary adenomas.Methods1. Patient Seleetion:Tissue samples were obtained from the patients who underwent surgery in the Affiliated Hospital of Hebei University from January,2007 to October,2010. The total number of tissue samples was 64,including 29 males and 37 females. All diagnoses of these cases were verified by immunohistochemieal pathology.According to the illustration of images and observation in operations, cases were divided into 36 invasive cases and 28 noninvasive cases.2. InununohistoehemistryThe expression of COX-2,MMP-9 and VEGF in invasive and noninvasive pituitary tumors were detected by using the immunohistochemistry of streptavidin biotin peroxidase protein A (SP) method.3. ResultdeterminationThe positive staining of COX-2 is brown or brown yellow partieles located in the cytoplasm and nuclear membrane.The positive staining of MMP-9 or VEGF is brown yellow particles located in cytoplasm. We observed five fields randomly each slice view of the tumor cells in the high power field (x400), calculated 200 immunoreactive tumor cells in the cell percentage.according to COX-2, MMP-9 and VEGF-positive cells in the color intensity and scope of the evaluation:â‘ negative (-):no positive staining.â‘¡weak positive (+):the namber of positive cells was less than 25% or slightly stained.â‘¢moderately positive (++): the namber of positive cells was from 26% to 50% or slightly stained deep.â‘£strongly positive (+++):the namber of positive cells was more than 50% or deep stained. Conparison: we used the positive biopsy for gastric cancer as the positive control and the PBS instead of primary antibody as negative control.Results1. Immunohistochemistry results:1). The rates of strongly positive expression of COX-2 in invasive and noninvasive cases were 52.8% and 10.7% respectively, the positive rates were 92.7% and 57.1%, the difference was significant both (respectively, x2=9.08, P<0.05 and x2= 11.75, P<0.05), the differences were statistically significant.2). The rates of strongly positive expression of VEGF in invasive and noninvasive cases were 55.6% and 14.3% respectively, the positive rates were 94.4% and 53.5%. Analysis of variance test, invasive and non-invasive pituitary tumor VEGF expression were significant differences (respectively, x2=9.27, P<0.05 and x2= 11.32, P<0.05), the differences were statistically significant.3). The rates of strongly positive expression of MMP-9 in invasive and noninvasive cases were 50.0% and 14.3% respectively, the positive rates were 86.1% and 50.0%, the difference was significant both (respectively, x2=9.06, P<0.05 and x2=10.91, P<0.05), the differences were statistically significant.2. The correlation analysis:The result of pearson correlation analysis showed that the expression in invasive pituitary of COX-2 and MMP-9 was positively correlated (rs=0.367, P<0.05), COX-2 and VEGF was positively correlated (rs=0.511, P<0.01), MMP-9 and VEGF expression was positively correlated (rs=0.776, P<0.01). The protein expression of COX-2, MMP-9 and VEGF in noninvasive pituitary adenomas was not related (P> 0.05).Conclusion1. The portein expression of COX-2, MMP-9, VEGF in the invasive and non-invasive pituitary adenomas are significant differences. The protein expressions of COX-2, MMP-9, VEGF in invasive pituitary adenomas was significantly higher than those in non-invasive pituitary adenomas.2. The invasive growth of pituitary adenoma may has connected with the high expression of COX-2, MMP-9, VEGF in tumor invasion and growth process.The high expression of COX-2 increased the expression of VEGF and promote the expression of MMP-9, the expression of VEGF and MMP- 9 promote each other. The three work together to promote the invasive growth of pituitary adenomas.3. It can served of COX-2, MMP-9, VEGF as a judge of invasiveness of the pituitary growth indicators.