The Expression Of Matrix Metalloproteinase-2,9 And Their Tissue Inhibitor-1,2 In Human Pituitary Adenomas

Pituitary adenomas are commonly intracranial neoplasms, which are benign in histology. However,about one -third of them,which are called as invasive pituitary adenomas, show malignant biological behavior , invading the cavernous sinus and surrounding bones, so it is difficult to resect them completely and the tumors recur frequently after operation. The pathogenesis of invasive pituitary adenomas isn' t clear at present,and their diagnosis is indirectly made mostly dependent on radiological manifestation. Tumor invasion is a cascade of proteolysis. In the course, degradation of extracellular matrix(ECM) is the characteristic of tumor invasion. Matrix metalloproteinases ( MMPs) are a family of Zn2 + - dependent endopeptidases, which are capable of degrad-ing essentially all of components of ECM except polysaccharide. MMP- 2 and MMP - 9 belong to the type IV collagenases, involved in the processes of tumor growth, invasion and metastasis. The main function of MMP - 2 and MMP - 9 is to hydrolyze ECM, that enables tumor cells to invade the surrounding tissues. The activity of MMP - 2 and MMP - 9 is regulated by their specific inhibitors, tissue inhibitor of matrix metalloproteinase(TIMP) - 1 and 2. TIMP - 1 inhibits the activity of MMP - 9 selectively while TIMP - 2 inhibits the activity of MMP - 2 selectively. An imbalance between MMPs and TIMPs can be found in many kinds of tumors. In this study, immunohistochemistry assay was used to research the expression of MMP -2^ MMP -9,, TIMP-1 and TIMP - 2 in pituitary adenomas to evaluate the relationship between the four indexes and invasiveness of pituitary adenomas. The aim of this study is to dissus the mechanism of invasion of pituitary adenomas , and to search the corresponding moleculobiological markers for biological behavior, clinical treatment and prognosis judgement of invasive pituitary adenomas.Materials and Methods: ( 1) Fifty - one surgically resected pituitary adenoma samples, induding 31 invasive pituitary adenomas and 20 noninvasive pituitary adenomas, and 8 normal anterior pituitary glands were collected. All of the tissues were fixed in 10% neutral formalin and enbedded in paraffin. (2) Streptavidin -Peroxidase(S -P) immunostaining technique was used to examine the expression of MMP- 2, MMP - 9, TIMP -1 and TIMP - 2 in all of the tissues. (3) Statis-tical analysis;the SAS 8. 2 software wrap was used, a =0. 05 was the level of test.RESULTS: ( 1) In normal anterior pituitary glands, noninvasive and invasive pituitary adenomas, the positive rates of MMP - 2 were 62. 5% (5/8) ^80% (16/20) and 87. 1% (27/31) respectively. An increasing tendency was found in the expression level of MMP ?2 from normal anterior pituitary glands to noninvasive and invasive pituitary adenomas, but there was no significant difference among the three groups ( P >0.05) . In the three groups,the positive rates of MMP -9 were 37. 5% (3/8) A50% (10/20) and 80. 6% (25/31) respectively. The expression level of MMP -9 in invasive pituitary adenomas was significantly higher than that in noninvasive pituitary adenomas and normal anterior pituitary glands( P <0.05) ,but there was no significant difference between the two latters ( P > 0. 05 ). In functioning and nonfunctioning pituitary adenomas the positive rates of MMP - 2 were 92.6% (25/27) and 75% (18/24) respectively, and there was no significant difference in the expression level of MMP - 2 between the two groups. In the two groups, the positive rates of MMP - 9 were 74. 1% (20/27) and 62. 5% ( 15/24) respectively, and there was no significant difference in the expression level of MMP - 9 between them ( P >0.05). (2)In normal anterior pituitary glands,noninvasive and invasive pituitary adenomas,the positive rates of TIMP - 1 were 100% (8/8) J5% (15/20) and 41. 9% (13/31) respectively. K clear decreasing tendency was found in the expression level of TIMP - 1 fromnormal anterior pitritary glands to noninvasive and invasive pituitary adenomas,and there was significant difference between invasive pituitary aden...