HYALURONAN DEPOSITION IN LIPOSARCOMA IS CORRELATED WITH THE GRADE OF MALIGNANCY

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Introduction Liposarcoma is common soft tissue sarcomas and is remarkable because of its variable histological picture ranging from well-differentiated lipoma-like to pleomorphic neoplasms. Among these histological variants, progressive cell migration is a central aspect of the pathophysiology of high grade malignant liposarcoma. Hyaluronan is one of the extracellular matrix (ECM) components, and has been known to play a significant role in cell proliferation and cell motility. The purpose of this study, is to determine the relationship of hyaluronan accumulation and malignant phenotypes of human liposarcoma. Methods Sixteen patients with histopathologically proven liposarcoma, 6 cases of pleomorphic, 6 of myxoid and 4 of well-differentiatied liposarcoma, had surgical treatment at our hospital. Three cases of lipoma were also obtained. Resected specimens were embedded in paraffin, prepared for the immunohistochemical analysis with biotinylated hyaluronic acid binding protein (HABP) for hyaluronan. Staining pattern was evaluated, and the statistically analyzed using chi-spuare test. Other part of the specimens was used for the isolation of total RNA, and subjected for RT-PCR to detect mRNA expression of hyaluronan synthase (HAS). Results Immunohistochemistry: HABP staining for hyluronan demonstrated the prominent hyaluronan accumulation in ECM of pleomorphic liposarcoma, whereas weak HABP positive staining was observed in ECM of well-differentiated liposarcoma and lipoma. These results were consistent with all samples. The staining pattern of HABP was significantly different (p<0.05) between each group. RT-PCR analysis: HAS2 and HAS3 mRNA expression were detected in all samples, however HAS1 could not be detected. Semi-quantitative analysis normalized by GAPDH indicated that both HAS2 and HAS3 mRNA levels were upregulated in pleomorphic liposarcoma. Discussion A number of studies have suggested that hyaluronan is involved in cell proliferation, motility and metastasis of tumors. This study demonstrated that hyaluronan expression were enhanced in pleomorphic forms, which is more progressive forms than well-differntiated forms, suggesting hyaluronan plays a significant role in tumor progression. In liposarcoma, to analyze the regulation of hyaluronan production will be one of the important ways to study the inhibition of tumor progression, invasion and metastasis.
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HYALURONAN DEPOSITION IN LIPOSARCOMA IS CORRELATED WITH THE GRADE OF MALIGNANCY

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