基质金属蛋白酶MMP-9、2及其抑制物TIMP-1、2在侵袭性垂体腺瘤生物学行为中的意义

Role of Matrix Metalloproteinases-9, 2 and Their Inhibitor-TIMP-1, 2 in Invasive Pituitary Adenomas Biological Behavior

背景与目的:通常垂体腺瘤在组织学上属良性肿瘤,但仍有部分肿瘤侵犯周围组织,形成侵袭性肿瘤,垂体腺瘤侵袭的生物学机制尚不清楚。垂体腺瘤血管丰富,而血管形成与肿瘤侵袭都需要细胞外基质成份的降解和细胞移动,这一过程中基质金属蛋白酶(matrixmetalloproteinases,MMP)和它们的天然抑制物-组织金属蛋白酶抑制剂(tissueinhibitorsofmetalloproteinases,TIMP)有可能起着关键作用。本研究拟通过检测MMP-9和MMP-2及其抑制因子TIMP-1和TIMP-2在非侵袭性垂体瘤和侵袭性垂体瘤中的表达,探讨垂体腺瘤的侵袭机制。方法:收集垂体瘤手术切除标本61例,分为侵袭组(49例)和非侵袭组(12例)。采用免疫组织化学SP法检测,并根据阳性细胞占肿瘤细胞总数的比率进行半定量非参数检验分析。结果:MMP-9、TIMP-1、MMP-2和TIMP-2在侵袭性垂体瘤中表达的阳性率分别为95.9%(47/49),57.1%(28/49),75.5%(37/49),和89.8%(44/49);在非侵袭性垂体瘤中阳性率分别为100%(12/12),91.7%(11/12),66.7%(8/12)和91.7%(11/12)。TIMP-1和TIMP-2的表达在侵袭性垂体瘤组明显少于非侵袭性垂体瘤组,(P<0.05);MMP-2在侵袭性垂体瘤组有增加的趋势,但无统计学意义,(P>0.05)。

Background & Objective:Usually pituitary adenomas are histological benign and grow slowly, but a proportion of them will become locally aggressive, and develop into invasive pituitary adenomas. The reasons for these differences in tumor behavior are poorly understood. Pituitary adenomas are abounding blood vessels. Angiogenesis and tumor invasion both require degradation of the extracellular matrix components to allow cell migration. The matrix metalloproteinases (MMPs) and their nature inhibitors the tissue inhibitors of metalloproteinases (TIMPs) may play a central role in these processes. The aggressive mechanism of pituitary adenomas was studied through investigating the expression of MMP 9, MMP 2,TIMP 1, and TIMP 2 in both invasive and non invasive adenomas. Methods:Sixty one surgical removed pituitary adenomas (forty nine cases invasive and twelve non invasive adenomas) were investigated. Immunohistochemistry staining (SP method) was used to detect the expression of MMP 9, MMP 2,TIMP 1, and TIMP 2 in two groups. The results were treated with semi quantitative method and analyzed by using non parameter rank sum test. Results:Immunohistochemical staining of tumor cells for MMP 9,TIMP 1,MMP 2,and TIMP 2 were noted 95 9%(47/49), 57 1%(28/49),75 5%(37/49) and 89 8%(44/49) in invasive adenomas,and 100%(12/12),91 7%(11/12),66 7%(8/12), and 91 7%(11/12) in non invasive adenomas,respectively. Invasive tumors were significantly less expressing TIMP 1 and TIMP 2 (P< 0 05). There was no significant difference for MMP 9 or MMP 2 between invasive and non invasive groups (P >0 05). Conclusions:TIMP 1 and TIMP 2 may play a key role in invasive pituitary adenomas to biological behavior.