ACCUMULATION OF INTER-α-TRYPSIN INHIBITOR CHAINS IN HUMAN BENIGN AND MALIGNANT LIPOMATOUS TUMORS. :

The inter-α-trypsin inhibitor (ITI) is one of the plasma proteinase inhibitors composed of two heavy chains (HC1 and HC2) and bikunin. Bikunin also composes pre-α-trypsin inhibitor (PαI) with one heavy chain (HC3). The potential roles of these proteins in tumor invasion have been suspected concerning their interactions with extracellular matrix and their protease inhibitory activity. Liposarcoma is remarkable because of its variable histological findings ranging from welldifferentiated and myxoid tumors to extremely cellular, pleomorphic neoplasms. We hypothesized that ITI proteins expression may be changed in benign and various malignant lipomatous tumors. The study was based on 28 tumors operated at Nagoya University Hospital. Resected tumors were diagnosed pathologically, 7 with pleomorphic liposarcoma, 5 with myxoid, 6 with well-differentiated, 10 with lipoma. The specimen were invesitgated with immunohistochemistry using anti-ITI, -bikunin, -HC3 polyclonal antibodies as primary antibody, and the staining was scored as weak (no intense signal), or moderate (<50% with intense signal), or strong (>50% with intense signal). Statistical analysis was performed with Chi-squared test. The correlations of staining intensities were analyzed between 2 groups; lipoma and well-differentiated liposarcoma versus myxoid and pleomorphic liposarcoma. The intensity of bikunin expression was significantly higher in relatively higher malignant tumors than benign and low malignant tumors (χ2=6.7 , p<0.01). ITI positivity also correlated significantly to grade of malignancy (χ2=4.9 , p<0.05). Total RNA was isolated with TRIzol, and subjected to RT-PCR analysis using the specific primers for bikunin, HC1, HC2 and HC3. Any products of ITI chains could not be detected using total RNA isolated from lipomatous tumors. These results showed that ITI proteins exogeneously accumulated in lipomatous tumors, and may play important role of in the patho genesis of these tumors.