Alford Stephanie H, Vrana Michael S, Waite Lindsay, Heim-Hall Josefine, Sylvia Victor L, Williams Ronald P
Department of Orthopaedics, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3901, USA.
Oncol Rep. 2007 Dec;18(6):1529-36.
Soft tissue sarcomas comprise a heterogeneous group of mesenchymal tumors with varying biological behavior ranging from indolent tumors with no or minimal metastatic risk to aggressive and frequently metastasizing tumors. Among the more common aggressive adult soft tissue sarcomas are malignant fibrous histiocytoma, synovial sarcoma and liposarcoma. Matrix metalloproteinases are enzymes which perform a homeostatic role in mesenchymal tissue and function in both tumorigenesis and metastasis. The objectives of this study are to determine the presence and relative quantity of matrix metalloproteinases (MMPs) -1, -2, -8, -9, and -13; extracellular matrix metalloproteinase inducer (EMMPRIN); and tissue inhibitors of matrix metalloproteinases (TIMP)-1 and -2 in high grade soft tissue sarcoma tumor specimens using real-time PCR. The second objective is to determine if a relationship exists between quantity of EMMPRIN, MMPs, and TIMPs expressed in tumor tissue and disease-free survival. One hundred and forty patients diagnosed with high grade soft tissue sarcomas between 1995-2003 were identified. Tissue blocks and histologic slides were acquired for 41 specimens. Tumor specimens included 29 malignant fibrous histiocytomas, 3 liposarcomas and 11 synovial sarcomas. RNA was extracted and RT-PCR was performed in triplicate. No significant differences were found between the three types of high grade soft tissue sarcomas studied and the expression of MMPs. Interestingly, no relationship was found between high or low levels of MMPs when compared with disease-free survival. Our data support other research which finds variable correlation between MMP expression in soft tissue sarcomas and disease-free survival. We assert that the difference in correlation between MMP expression in carcinomas and sarcomas and disease-free survival is based on the vast phenotypic and genotypic difference between the cells of origin.
软组织肉瘤是一组异质性的间充质肿瘤,其生物学行为各异,从无转移风险或转移风险极小的惰性肿瘤到侵袭性强且常发生转移的肿瘤。在较为常见的侵袭性成人软组织肉瘤中,有恶性纤维组织细胞瘤、滑膜肉瘤和脂肪肉瘤。基质金属蛋白酶是在间充质组织中发挥稳态作用且在肿瘤发生和转移过程中起作用的酶。本研究的目的是使用实时聚合酶链反应(PCR)确定基质金属蛋白酶(MMPs)-1、-2、-8、-9和-13、细胞外基质金属蛋白酶诱导剂(EMMPRIN)以及基质金属蛋白酶组织抑制剂(TIMPs)-1和-2在高级别软组织肉瘤肿瘤标本中的存在情况和相对数量。第二个目的是确定肿瘤组织中EMMPRIN、MMPs和TIMPs的表达量与无病生存期之间是否存在关联。确定了1995年至2003年间被诊断为高级别软组织肉瘤的140名患者。获取了41个标本的组织块和组织学切片。肿瘤标本包括29个恶性纤维组织细胞瘤、3个脂肪肉瘤和11个滑膜肉瘤。提取RNA并进行三次重复的逆转录PCR。在所研究的三种高级别软组织肉瘤类型与MMPs的表达之间未发现显著差异。有趣的是,与无病生存期相比,MMPs水平的高低之间未发现关联。我们的数据支持其他研究,这些研究发现软组织肉瘤中MMP表达与无病生存期之间存在不同程度的相关性。我们认为,癌和肉瘤中MMP表达与无病生存期之间相关性的差异是基于起源细胞之间巨大的表型和基因型差异。