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


METHODS
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.
Yamamoto
Tetsuji
T
Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. yamatetu@med.kobe-u.ac.jp
Akisue
Toshihiro
T
Marui
Takashi
T
Fujita
Ikuo
I
Matsumoto
Keiji
K
Hitora
Toshiaki
T
Kawamoto
Teruya
T
Nagira
Keiko
K
Nakatani
Tetsuya
T
Kurosaka
Masahiro
M
D030201:Activin Receptors, Type I / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D018219:Histiocytoma, Benign Fibrous / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D012983:Soft Tissue Neoplasms / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3
D020033:Protein Isoforms; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II