Relations Between Expression Of Pituitary Tumor Transforming Gene (PTTG), MatrixetalloProteinase-2, 9(MMP-2, MMP-9) And Invasion In Pituitary Adenomas

Background and Objective:Pituitary adenoma is common among the central nervous system, with the fre-quency is about 10%. It is lower than neurogliocytoma and meningeoma in thebrain. 1/3 of them, according to histological classification are benign neoplasms,but biologically act as malignant ones, are defined as invasive pituitary adenoma.Invasive pituitary adenoma can grow up locally and encroach on diaphragma se-llae, dura skull, bone, nerves, cavernous sinus and adjacent vessels and brain. In-vasive pituitary adenoma has a poorer prognosis than non-invasive tumors beca-use they are difficult to remove completely. The therapy effect is relative to theinvasiveness of pituitary adenoma. Because invasive pituitary adenoma is easyto lead to postoperative recurrence, it is important to research the factors whichare relative to the invasiveness of pituitary adenoma.Recently a new oncogene -pituitary tumour transforming gene (PTTG) wasisolated. It is highly expressed in the vast majority of sporadic pituitary adeno-mas but is present only at low levels in the normal pituitary. PTTG has an impo-rtant role in tumor growth and invasiveness. Heaney considers that PTTG is im-portant not only to pituitary tumour generation but also to the judgement of inv-asiveness of pituitary adenoma.In the process of the tumors' invasive growth, matrix metalloproteinases playimportant roles. Matrix metalloproteinases are a family of enzymes whose mainfunction is degrading of the extracellular matrix. MMPs have been defined fun-ctionally as having the following characteristics: they are proteinases which de-grade at least one component of the extracellular matrix;they contain a zinc ionand are inhibited by chelating agents;they are secreted in a latent form, requiri-ng activation for proteolytic activity;they share common amino acid sequences.MMP-2 (gelatinase A) and MMP-9 (gelatinase B) are the main matrix metallop-roteinases in decomposing collagen including type IV and V in the matrix, beca-use collagen IV not only exists in the ECM, but also is one of the most importa-nt components of the basement membrane. Matrix metalloproteinases can degr-ade extracellular matrix and destroy basement membrane to accelerate angioge-nesis of tumors. It depends on the researches that the release of MMP-2 andMMP-9 has relations to invasiveness of malignant tumors.The courses of invasiveness of pituitary adenoma are the changes in gene andthe changes of components of the extracellular matrix. Using immunohistoche-mical SP staining, I detect the relation of PTTG, MMP-2 and MMP-9 to invasi-veness of pituitary adenomas and detect the clinical meaning of these factors.Objective: To detect the expression of pituitary tumor transforming gene(PTTG),matrix metalloproteinase-2, 9(MMP-2, MMP-9) relate to invasion inpituitary adenomas.Methods: 63 pituitary adenoma specimens removed in our department fromMarch, 2004 to Nov, 2005 were collected, all fixed with 4% formalin and thenp-araffin embedded. All specimens were divided into invasive group(22 cases)and noninvasive group (41 cases). Expression of PTTG protein, MMP-2 andMMP-9 in 63 slices of specimens were examined by immunohistochemistry.Finally we analyzed the relation between expression of PTTG protein, MMP-2and MMP-9 and invasiveness of the pituitary adenomas.Results:1. The positive expression rate of PTTG in invasive pituitary adenomas andnon-invasive pituitary adenomas is (20/22), (19/41) respectively. There is signi-ficant difference among them (X2=12.06, P<0.01).2. The positive expression rate of MMP-2 in invasive pituitary adenomas andnon-invasive pituitary adenomas is (10/22), (5/41) respectively. There is signif-icant difference among them (X2=8.73, P<0.01).3. The positive expression rate of MMP-9 in invasive pituitary adenomas andnon-invasive pituitary adenomas is (14/22), (9/41) respectively. There is signif-icant difference among them (X2=10.73, P<0.01).Conclusions:1. The expression of PTTG, MMP-2, MMP-9 in invasive pituitary adenomasis higher than that in non-invasive pituitary adenomas.2. PTTG, MMP-2, MMP-9 play important roles in invasiveness of pituitaryadenomas. The expression of them could help make treatment plans so that theycould make the therapeutic effect higher.