Expression of betacellulin, heparin-binding epidermal growth factor and epiregulin in human malignant fibrous histiocytoma

Anticancer Res. 2004 May-Jun;24(3b):2007-10.


Background: Heparin-binding epidermal growth factor (HB-EGF), betacellulin (BTC) and epiregulin (EPR) are members of the EGF system and involved in the cell growth of various epithelial malignancies. There have been no reports on the HB-EGF, BTC and EPR expression in mesenchymal malignancies of fibrohistiocytic origin including malignant fibrous histiocytoma (MFH).

Materials and methods: We investigated the expression of HB-EGF, BTC, EPR and EGF-receptor (EGF-R) in 43 human MFH tissue samples using immunohistochemical techniques.

Results: Positive immuno-reactivity for HB-EGF, BTC, EPR and EGF-R was identified in 28 (65%), 7 (16%), 43 (100%) and 36 (84%) out of the 43 MFH cases analyzed, respectively. Coexpression of HB-EGF/BTC, BTC/EPR and HB-EGF/EPR was observed in 6 (14%), 7 (16%) and 28 (65%) of the MFHs, respectively. Coexpression of HB-EGF/EGF-R, BTC/EGF-R and EPR/EGF-R was observed in 25 (58%), 6 (14%) and 36 (84%) of the MFHs, respectively.

Conclusion: These results revealed that HB-EGF, BTC and EPR are expressed not only by epithelial tumor cells, but also by MFH cells. It is suggested that HB-EGF and EPR might be more important tumor growth regulators of MFH through autocrine or paracrine pathways, when compared with BTC.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Betacellulin
  • Epidermal Growth Factor / biosynthesis*
  • Epiregulin
  • ErbB Receptors / biosynthesis
  • Female
  • Heparin-binding EGF-like Growth Factor
  • Histiocytoma, Benign Fibrous / metabolism*
  • Humans
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins / biosynthesis*
  • Male
  • Middle Aged


  • BTC protein, human
  • Betacellulin
  • EREG protein, human
  • Epiregulin
  • HBEGF protein, human
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Epidermal Growth Factor
  • ErbB Receptors