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Expression of Transforming Growth Factor ß Isoforms and Their Receptors in Malignant Fibrous Histiocytoma of Soft Tissues

¹ Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe; and ² Department of Orthopaedic Surgery, Hyogo Medical Center for Adults, Akashi, Japan

Purpose: Transforming growth factor ß (TGF-ß) is a multifunctional growth factor that variably affects proliferation, differentiation, and extracellular matrix formation. Little information is currently available on the TGF-ß expression in malignant fibrous histiocytoma (MFH). The aims of the present study were to investigate the expression of TGF-ß isoforms and their receptors in human MFH specimens.

Experimental Design: The expression of TGF isoforms, and TGF-ß receptors (TGF-ßR1 and -ßR2) were immunohistochemically evaluated in 43 paraffin-embedded MFH specimens. Furthermore, the correlation of the TGF-ß and receptor expression with tumor proliferative activity assessed by MIB-1 indices was analyzed.

Results: Positive immunoreactivity for TGF-ß1, -ß2, and -ß3 was identified in tumor cells of 42, 40, and 38 of the 43 MFHs, respectively. In each TGF-ß isoform immunostaining, the specimens were divided into two groups based on the number of positive tumor cells: those with low (<25%) and those with high (25%) immunoreactivity. There were no statistically significant differences in the MIB-1 indices between the two groups. Positive immunoreactivity for TGF-ßR1 and -ßR2 was identified in tumor cells of 36 and 24 of the MFHs, respectively. The specimens were divided into two groups based on their receptor expression patterns: those with both TGF-ßR1- and -ßR2-positive immunoreactivity (n = 23), and those with both or either TGF-ßR1- and -ßR2-negative immunoreactivity (n = 20). The MIB-1 indices in the both-TGF-ßR1- and -ßR2-positive group were significantly higher than those in the other group (P = 0.0102). There was no significant difference in pulmonary metastasis ratios between the two groups.

Conclusions: These findings strongly suggest an association of the TGF-ß ligand/receptor system with a significantly higher MIB-1 index in human MFHs. Investigation of the TGF-ßR1 and -ßR2 coexpression might be useful in predicting tumor behavior of MFHs.