The expression levels and the differential expression of transforming growth factor-beta receptors in dermatofibroma and dermatofibrosarcoma protuberans

Br J Dermatol. 2006 May;154(5):919-25. doi: 10.1111/j.1365-2133.2005.06904.x.

Abstract

Background: Dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) are benign and intermediate malignant fibrotic dermal tumours, respectively. The contribution of transforming growth factor (TGF)-beta has been implicated in the progression of sclerosis in fibrotic diseases.

Objectives: To investigate the expression of TGF-beta receptors in these fibrotic tumours.

Methods: We examined the expression levels of TGF-beta type I and type II receptors (TGFbeta-RI and TGFbeta-RII) in DF and DFSP using in situ hybridization and immunohistochemical analysis. We also examined the expression of TGF-beta1 and collagen type I using immunohistochemical analysis.

Results: We detected strong expression of TGFbeta-RI and TGFbeta-RII on epidermis and epidermal appendages, moderate expression in vascular endothelial cells, smooth muscle cells and neural tissues, and weak expression in fibroblasts in normal skin sections. The expression levels of TGFbeta-RI and TGFbeta-RII were elevated in the tissue sections of DF in comparison with normal dermal sections using in situ hybridization and immunohistochemical staining. Furthermore, the expression of TGFbeta-RI and TGFbeta-RII was strong in spindle-shaped cells around DF. The expression of TGFbeta-RI and TGFbeta-RII was decreased in DFSP in comparison with DF, and their expression was found to be homogeneous in each DFSP tumour cell. The staining for TGF-beta1 was found prominently on matrix and spindle-shaped tumour cells of DF, and peripheral regions of DFSP. Weak expression of TGF-beta1 was found on normal skin or tumour cells in the central part of DFSP. Type I collagen expression was found on spindle-shaped tumour cells in DF, but not in tumour cells of DFSP.

Conclusions: These results suggest the possibility that TGF-beta signalling may contribute to the fibrosis around DF, and that TGF-beta receptors may play important roles in TGF-beta signalling. The expression patterns of TGFbeta-RI and TGFbeta-RII may be helpful in distinguishing these diseases.

MeSH terms

  • Activin Receptors, Type I / genetics
  • Activin Receptors, Type I / metabolism
  • Adult
  • Biomarkers, Tumor / metabolism
  • Collagen Type I / metabolism
  • Dermatofibrosarcoma / diagnosis
  • Dermatofibrosarcoma / metabolism*
  • Diagnosis, Differential
  • Female
  • Histiocytoma, Benign Fibrous / diagnosis
  • Histiocytoma, Benign Fibrous / metabolism*
  • Humans
  • In Situ Hybridization
  • Male
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Protein Serine-Threonine Kinases
  • RNA, Messenger / genetics
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / metabolism*
  • Skin / metabolism
  • Skin Neoplasms / diagnosis
  • Skin Neoplasms / metabolism*
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • Collagen Type I
  • Neoplasm Proteins
  • RNA, Messenger
  • Receptors, Transforming Growth Factor beta
  • Protein Serine-Threonine Kinases
  • Activin Receptors, Type I
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II