Kubo M, Ihn H, Yamane K, Tamaki K
Department of Dermatology, Faculty of Medicine, University of Tokyo, Mita Hospital, Tokyo, Japan.
Br J Dermatol. 2006 May;154(5):919-25. doi: 10.1111/j.1365-2133.2005.06904.x.
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.
To investigate the expression of TGF-beta receptors in these fibrotic tumours.
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.
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.
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.
皮肤纤维瘤（DF）和隆突性皮肤纤维肉瘤（DFSP）分别是良性和中间型恶性的纤维化皮肤肿瘤。转化生长因子（TGF）-β在纤维化疾病的硬化进展中发挥了作用。
研究TGF-β受体在这些纤维化肿瘤中的表达。
我们使用原位杂交和免疫组织化学分析检测了DF和DFSP中TGF-βⅠ型和Ⅱ型受体（TGFβ-RⅠ和TGFβ-RⅡ）的表达水平。我们还使用免疫组织化学分析检测了TGF-β1和Ⅰ型胶原的表达。
在正常皮肤切片中，我们检测到TGFβ-RⅠ和TGFβ-RⅡ在表皮和表皮附属器上强表达，在血管内皮细胞、平滑肌细胞和神经组织中中度表达，在成纤维细胞中弱表达。使用原位杂交和免疫组织化学染色，与正常真皮切片相比，DF组织切片中TGFβ-RⅠ和TGFβ-RⅡ的表达水平升高。此外，DF周围的梭形细胞中TGFβ-RⅠ和TGFβ-RⅡ的表达较强。与DF相比，DFSP中TGFβ-RⅠ和TGFβ-RⅡ的表达降低，并且在每个DFSP肿瘤细胞中其表达是均匀的。TGF-β1染色在DF的基质和梭形肿瘤细胞以及DFSP的周边区域显著可见。在DFSP中央部分的正常皮肤或肿瘤细胞上发现TGF-β1弱表达。在DF的梭形肿瘤细胞上发现Ⅰ型胶原表达，但在DFSP的肿瘤细胞中未发现。
这些结果提示TGF-β信号传导可能导致DF周围纤维化，并且TGF-β受体可能在TGF-β信号传导中发挥重要作用。TGFβ-RⅠ和TGFβ-RⅡ的表达模式可能有助于区分这些疾病。
