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.

• Authors: Tetsuji Yamamoto, Toshihiro Akisue, Takashi Marui, Ikuo Fujita, Keiji Matsumoto, Toshiaki Hitora, Teruya Kawamoto, Keiko Nagira, Tetsuya Nakatani, Masahiro Kurosaka
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 10 Issue 17 Pg. 5804-7 (Sep 01 2004) ISSN: 1078-0432 [Print] United States
• PMID: 15355909 (Publication Type: Journal Article)

Chemical References

• Protein Isoforms
• Receptors, Transforming Growth Factor beta
• TGFB1 protein, human
• TGFB2 protein, human
• Transforming Growth Factor beta
• Transforming Growth Factor beta1
• Transforming Growth Factor beta2
• Transforming Growth Factor beta3
• Protein Serine-Threonine Kinases
• Activin Receptors, Type I
• Receptor, Transforming Growth Factor-beta Type I
• Receptor, Transforming Growth Factor-beta Type II

Topics

• Activin Receptors, Type I (metabolism)
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Female
• Histiocytoma, Benign Fibrous (metabolism, pathology)
• Humans
• Immunoenzyme Techniques
• Male
• Middle Aged
• Protein Isoforms
• Protein Serine-Threonine Kinases
• Receptor, Transforming Growth Factor-beta Type I
• Receptor, Transforming Growth Factor-beta Type II
• Receptors, Transforming Growth Factor beta (metabolism)
• Soft Tissue Neoplasms (metabolism, pathology)
• Transforming Growth Factor beta (metabolism)
• Transforming Growth Factor beta1
• Transforming Growth Factor beta2
• Transforming Growth Factor beta3