Increased expression of membrane-type matrix metalloproteinase-1 is correlated with poor prognosis in patients with osteosarcoma.
Increased expression of membrane-type matrix metalloproteinase-1 is correlated with poor prognosis in patients with osteosarcoma.
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DOI：
10.3892/ijo.28.1.33
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发表时间：
2006
影响因子：
5.2
通讯作者：
Mitsutoshi Uchibori;Y. Nishida;T. Nagasaka;Yoshihisa Yamada;Keisuke Nakanishi;N. Ishiguro
中科院分区：
文献类型：
--
作者：
Mitsutoshi Uchibori;Y. Nishida;T. Nagasaka;Yoshihisa Yamada;Keisuke Nakanishi;N. Ishiguro
大量研究表明，基质金属蛋白酶（MMP）过表达与多种肿瘤的预后相关。本研究旨在探讨基质金属蛋白酶的表达是否与骨肉瘤的预后相关。采用免疫组化法检测47例骨肉瘤组织中MMP-2、MMP-9、MT 1-MMP和TIMP-2的表达。采用Kaplan-Meier法分析染色阳性率与预后的相关性，采用log-rank检验进行统计学分析。MMP-2、MT 1-MMP和TIMP-2的共定位通过荧光标记抗体的双重染色来确定。用明胶酶谱法检测了代表性组织中明胶酶的活性。MMP-2强阳性率为60%（28/47），MMP-9、MT 1- MMP和TIMP-2强阳性率分别为61%（29/47）、45%（21/47）和91%（43/47）。MT 1-MMP表达增高与总生存期预后不良显著相关（P=0.0480）。在MMP-2和MT 1-MMP均过表达的病例中，有预后不良的趋势（P=0.0969）。在36例接受新辅助化疗、肿瘤广泛切除和术后辅助化疗的患者中，MT 1-MMP表达增加是无病生存的显著负性预后因素（P=0.0143）。同时，MT 1-MMP和MMP-2的共同过表达显示出与无病生存率降低相关的趋势（P=0.0502）。在MT 1-MMP和MMP-2共同过表达的组织中观察到明胶酶活性增加。本研究的结果表明，MT 1-MMP的表达和骨肉瘤患者的肿瘤学结果的相关性，提示这些蛋白在骨肉瘤患者的预后意义。
Numerous studies have demonstrated a correlation of matrix metalloproteinase (MMP) overexpression with the prognosis of various kinds of cancer. The current study investigated whether the expression of MMPs is correlated with the prognosis of osteosarcoma. Expression levels of MMP-2, -9, MT1-MMP and TIMP-2 were examined immunohistochemically in samples from 47 patients with osteosarcoma. Correlation of the positivity of staining with prognosis was analyzed with the Kaplan-Meier method, and statistically analyzed with log-rank test. Co-localization of MMP-2, MT1-MMP and TIMP-2 was determined by double staining with fluorescence-conjugated antibodies. Activities of gelatinases in representative tissues were examined with gelatin zymography. MMP-2 was expressed strongly in 60% of cases (28/47), and MMP-9, MT1- MMP and TIMP-2 was strongly positive in 61% (29/47), 45% (21/47), and 91% (43/47), respectively. Increased MT1-MMP expression was associated significantly with poor prognosis in overall survival (P=0.0480). In cases of overexpression for both MMP-2 and MT1-MMP, there was a tendency for poor prognosis (P=0.0969). In 36 cases who underwent neoadjuvant chemotherapy, wide resection of the tumors and post-operative adjuvant chemotherapy, increased expression of MT1-MMP resulted in a significant negative prognostic factor for disease-free survival (P=0.0143). Also, co-overexpression of MT1-MMP and MMP-2 showed a tendency to correlate to the reduced disease-free survival (P=0.0502). Increased gelatinase activity was observed in tissues of co-overexpression of MT1-MMP and MMP-2. The results of this study demonstrate the correlation of MT1-MMP expression and the oncological outcome of osteosarcoma patients, suggesting the prognostic significance of these proteins in osteosarcoma patients.