基质金属蛋白酶-9和促血管生成素1、2与垂体腺瘤侵袭性的关系

The study on the association of MMP-9、Ang-1 and Ang-2 with tumor invasive behavior in human pituitary daenomas

目的研究基质金属蛋白酶-9(matrix metalloproteinases-9,MMP-9)和促血管生成素(angiopoietin,Ang-1和Ang-2)在垂体腺瘤中的表达与其侵袭性的相关性。方法选取垂体腺瘤手术标本40例,分侵袭组(11例)和非侵袭组(29例),应用逆转录—聚合酶链反应(RT-PCR)方法对垂体腺瘤标本MMP-9、Ang-1、Ang-2 mRNA的表达进行分析。免疫组化方法对垂体腺瘤标本中MMP-9、Ang-1、Ang-2的表达进行研究。结果 MMP-9 mRNA在侵袭性垂体腺瘤表达为1.513±0.28明显高于非侵袭性垂体腺瘤的0.883±0.245(t=4.61,P<0.05),Ang-2 mRNA在侵袭性垂体腺瘤表达为1.455±0.28明显高于非侵袭性垂体腺瘤的0.935±0.291(t=4.37,P<0.05)。MMP-9、Ang-2蛋白在侵袭性垂体腺瘤组中表达水平明显高于非侵袭性垂体腺瘤组(T=3.82,T=4.10,P<0.05)。非侵袭性腺瘤组织Ang-1 mRNA表达为1.263±0.389明显高于侵袭性垂体腺瘤的0.889±0.323(t=4.46,P<0.05),非侵袭性垂体腺瘤组Ang-1蛋白表达明显高于侵袭性垂体腺瘤组(T=5.53,P<0.05)。Ang-1和Ang-2表达呈负相关(r=-0.68,P<0.05),MMP-9、Ang-1与Ang-2在垂体腺瘤中的表达高低与患者性别、垂体瘤有无分泌功能无关。结论 MMP-9和Ang-2在侵袭性垂体腺瘤中的高表达及Ang-1在侵袭性垂体腺瘤中的低表达,可能与垂体腺瘤的侵袭性生长有关。

Objective To study the expression of matrix metalloproteinase 9 （ MMP-9）, Angiopoietin-1 （ Ang-1 ） and Angiopoietin-2 （Ang-2） in pituitary adenomas and explore their relationships with tumor invasive behavior. Methods The mRNA and protein expression levels of MMP-9, Ang-1 and Aug-2 were determined using RT-PCR assay and immuno- histoehemical technique in 40 pituitary adenoma tissues samples from surgery, respectively. The samples included 11 invasive pituitary adenomas and 29 non-invasive ones. Results The mRNA expression levels of MMP-9 were significantly higher in invasive pituitary adenomas than in non-invasive ones （ 1. 513 ± 0.28 vs 0. 883 ± 0. 245 ） （ t = 4. 61, P 〈 0. 05 ）. The mRNA expression levels of Ang-2 in invasive pituitary adenomas were higher than non-invasive ones （ 1. 455 ± 0. 28 vs O. 935 ± O. 291 ） （t = 4. 37, P 〈 0.05 ）. The protein expression levels of MMP-9 and Ang-2 were significantly higher in invasire pituitary adenomas than in non-invasive ones（ T = 3.82＆T =4. 10 ,P 〈 0. 05 ）. In contrast, the mRNA expression levels of Ang-I mRNA were higher in non-invasive pituitary adenomas than in invasive ones （ 1. 263 ：t： 0. 389 vs 0. 889 ＋ 0. 323 ） （ t = 4.46 ,P 〈 0. 05 ）. The protein expression levels of Ang-1 protein were higher non-invasive pituitary adenomas than in in- vasive ones （ T = 5.53 ,P 〈 0. 05 ）. Both Ang-2 and Ang-1 expression levels were negatively correlated with pituitary adeno- mas invasion （ r = - 0. 68,P 〈 0. 05 ）. There were no correlations of MMP-9, Ang-1 and Ang-2 with clinical features （ P 〉 0. 05 ）. Conclusions Our study suggests that the expression levels of MMP9, Ang-1 and Ang-2 may have a value to assess the invasive pituitary adenomas.