| Osteosarcoma(OS) is the most common primary malignant tumor of bone,comprising 20% of all such primary malignancies.Its hematogenous metastasis occurs more frequently and early. Pulmonary metastasis is the main fatal cause in patients with OS. Degradation of extracellular matrix (ECM) is a key step for metastasis. It depend mainly on ECM degrading enzymes especially matrix metalloproteinases 2(MMP-2) which plays an important role during tumor invasion and metastasis. MMP-2 is proteolytic enzyme capable of degrading ECM including collagen,gelatin,laminin,fibronect and proteoglycan and overexpresses in many kinds of tumor tissues. MMP-2 activity is modulated by its relative tissue inhibitor of metalloproteinases 2 (TIMP-2). Imbalance between MMP-2 and2002 fEfflçœMEifcg: _ MMP-z in TIMP-2TIMP-2 have been implicated in the invasive potential of many kinds malignant tumor. Both of them play a significant role in regulating angiogenesis as the process of new blood vessel formation. Up to now their expression and the correlation between them in OS have rarely been reported. In order to evaluate the role of MMP-2 and TIMP-2 in OS as well as their interaction, immunohistochemical SABC technique is applied to examine their expression in OS. It is expected that the study will help us to judge the metastatic potential of osteosarcoma and provide theoretical foundation for clinical therapy.Materials and Methods: By surgically resection 79 osteosarcoma samples histopathologically include 69 cases of high-grade and 10 cases of low-grade OS such as conventional parosteal osteosarcoma. There were 29 with Osteoblast osteosarcoma, 18 with fibroblasts osteosarcoma, 16 with Chondroblast osteosarcoma,3 with telangiectatic osteosarcoma, 3 with small cell osteosarcoma as subgroups of the high-grade group. All the tissue were fixed in 10% neutral formalin and embeded in paraffin. Immunohistochemical Strept Avidin-Biotin Complex (SABC) method was undertaken to determine the expressions of MMP-2 and TIMP-2. There is a statistical significance when P<0.05.Results: l.The positive staining of MMP-2 and TIMP-2 is mainly located in the cytoplasm of tumor cell. 2.The positive rate of MMP-2 was 79.7(55/69) in the high-grade group and 79.3%(23/29)> 77.8%(14/18^ 75%(12/16)^ 100%(3/3)> 100%(3/3) respectively in its subgroups described above. The positive rates of MMP-2 was 40%(4/10) in the low-grade group. The positive rate of TIMP-2 was 31.9%(22/69)in the high-grade group and 31%(9/29X 33.3%(6/18)>MMP-2 fl TIMP-231.3%(5/16) , 33.3%(l/3) > 33.3%(l/3) respectively in its subgroups.The positive rates of TIMP-2 in the low-grade group was 70%(7/10). There were significance differences(P<0.05) both in MMP-2 and TIMP between high-grade and low-grade groups. 3. Based on the Enneking system,79 cases osteosarcoma were divided into 3 groups stage I ,stage II ,stageIII.The positive rates of MMP-2 expression were 40% (4/10), 74.5% (41/55), 100% (14/14) respectively.The positive rates of TIMP-2 expression were 70%(7/10), 36.4% (20/55), 14.3% (2/14) respectively. There were significant differences(P<0.05) in MMP-2 and TIMP-2 expression between stage I and stagelll group. 4. The positive rates of MMP-2 expression in OS were 83.3% (40/48 ) and 61 .3% (19/31) respectively with and without soft tissue invasion, while the positive rates of TIMP-2 were 27.1% (13/48) and 51.6% (16/31) respectively.There were significant difference(P<0.05)in MMP-2 and TIMP-2 between the two groups. In the group with metastasis and that without metastasis, the positive rates of MMP-2 expression were 100%(15/15) and 68.8% (44/64) respectively and those of TIMP-2 were 13.3% ( 2/15 ) and 42.2% ( 27/64 ) .There were significant difference(P<0.05) in MMP-2 and TIMP-2 between the two groups. S.There were significant correlations between MMP-2 and TIMP-2 expression in osteosarcoma. 6. In 45 cases with positive MMP-2 and negative TIMP-2, 13 cases had metastasis and 34 cases had soft tissue invasion while no metastasis and 2 cases of soft tissue invasion occurr...
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