Expression of transforming growth factor beta isoforms and their receptors in malignant fibrous histiocytoma of soft tissues

Abstract

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

Experimental design: The expression of TGF isoforms, and TGF-beta receptors (TGF-beta R1 and -beta R2) were immunohistochemically evaluated in 43 paraffin-embedded MFH specimens. Furthermore, the correlation of the TGF-beta and receptor expression with tumor proliferative activity assessed by MIB-1 indices was analyzed.

Results: Positive immunoreactivity for TGF-beta1, -beta2, and -beta 3 was identified in tumor cells of 42, 40, and 38 of the 43 MFHs, respectively. In each TGF-beta 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-beta R1 and -beta R2 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-beta R1- and -beta R2-positive immunoreactivity (n = 23), and those with both or either TGF-beta R1- and -beta R2-negative immunoreactivity (n = 20). The MIB-1 indices in the both-TGF-beta R1- and -beta R2-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-beta ligand/receptor system with a significantly higher MIB-1 index in human MFHs. Investigation of the TGF-beta R1 and -beta R2 coexpression might be useful in predicting tumor behavior of MFHs.