Matrix metalloproteinase expression in high grade soft tissue sarcomas

Abstract

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.