CD44s、MMP-9、Ki-67的表达与骨肉瘤侵袭、转移、复发的关系

Expressions of CD44s,MMP-9,and Ki-67:Possible Association with Invasion,Metastasis,and Recurrence of Osteosarcoma

背景及目的:近期研究表明,细胞表面粘附分子CD44和基质金属蛋白酶类(MMPs)在多种肿瘤组织中有高水平表达,且与肿瘤的侵袭转移关系密切;Ki-67是一种细胞增殖核抗原,表示肿瘤细胞的增殖速率;但三者与骨肉瘤的局部侵袭、远处转移及术后是否复发之间的关系尚不清楚,本研究拟探讨细胞表面粘附分子标准型CD44蛋白(CD44s)以及基质金属蛋白酶-9(MMP-9)和细胞增殖核抗原(Ki-67)在骨肉瘤中的表达情况及其与骨肉瘤侵袭、转移、复发的关系。方法:采用免疫组织化学SP法检测了62例骨肉瘤(初发性骨肉瘤51例、复发性骨肉瘤11例,确诊时即伴有肺转移者9例、不伴有肺转移者53例)以及骨纤维结构不良和正常对照组织中CD44s、MMP-9、Ki-67的表达,并根据阳性瘤细胞占肿瘤细胞总数的比率进行半定量量化分析和非参数秩和检验。结果:CD44s、MMP-9、Ki-67在骨肉瘤中的阳性表达率分别为71.0%、75.8%和35.5%,与三种分子在骨良性病变和正常对照组织中的阳性表达率相比,其表达水平显著性升高(P值均小于0.05)。CD44s和MMP-9在初发性和复发性骨肉瘤之间的表达差异无显著性意义,但Ki-67在术后复发的骨肉瘤中的阳性率为81.8%,比初发性骨肉瘤中的阳性率显著性升高。CD44s和Ki-67在伴有肺转移的骨肉瘤中的阳性率分别为88.9%和66.7%。

Background &Objective:Recent research had showed that tumo r cell adhesion molecular CD44and matrix metalloproteinases(MMP )were expressed strongly in many tumo rs,and was associated closely with i nvasion and metastasis of the tumors.Ki-67was o ne of the proliferative markers,whi ch indicated the growth rate of tumor cells.However,the relationship among these markers and the invasion,metasta sis,and recurrence of osteosarcoma was unclear yet.In this research the authors stu died the expression of standard-type CD44(CD44s ),MMP-9,and Ki-67in osteosarcoma,and their relation to the invasion,metastasis,and recurrence of the tumor.Methods:Immunohistochemistry staining(SP method)was used to detect CD44s,MMP-9,and Ki-67in 62cases of osteosarcoma.Bon e benign disease or normal connective tissue were used a s the control.The results were treated with semi-quantitative method an d analyzed by using non-parameter rank sum test.Results:The positive rates of CD44s,MMP-9,a nd Ki-67in osteosarcoma were71.0%,75.8%,and 35.5%,respectively,which were significantly higher than that in control tissue.The positive rate of Ki-67in recurrent osteosarcoma w as 81.8%,which was significantly hi gher than that in primary tumor.CD44s and Ki-67positive rates were 88.9%and 66.7%respectively in osteosarcoma w ith lung metastasis,which were both significantly higher than that in osteosarcoma without lung metastasis.In poorly differentiated osteosarcoma positive rates of CD44s and MMP-9were 76.3%and 79.7%,respectively,which were significantly higher than that in well differe ntiated tumor.Spearman correlation analysis proved that the expression of CD44s,MMP-9,and Ki-67had significant r elation to another.Conclusions:Increase of CD44s,MMP-9,and Ki-67w ere involved in the growth and local i nvasion of osteosarcoma.The recurrence of osteosarcoma was associated with the pr oliferative rate of tumor cells.Whether there were early lung metastasis or not was affe cted by the amount of CD44s and the pro liferative rate of the tumor cell.The poorer differentiation of osteosarcoma ce lls,the higher level of CD44s and MMP -9.