The involvement of fibroblast growth factor receptor signaling pathways in dermatofibroma and dermatofibrosarcoma protuberans
The involvement of fibroblast growth factor receptor signaling pathways in dermatofibroma and dermatofibrosarcoma protuberans
复制标题
DOI：
10.2152/jmi.60.106
复制
发表时间：
2013-02-01
影响因子：
0.7
通讯作者：
Kubo, Yoshiaki
中科院分区：
文献类型：
--
作者：
Ishigami, Takeshi;Hida, Yasutoshi;Kubo, Yoshiaki
成纤维细胞生长因子（FGF）及其受体（FGFR）控制着广泛的生物学功能;然而，它们参与皮肤纤维瘤（DF）和隆突性皮肤纤维肉瘤（DFSP）的发病机制目前尚不清楚。在本研究中，我们首先通过检测DFSP中的融合COL 1A 1-PDGFB转录本来确认组织学诊断，并通过免疫组织化学分析来检测DF和DFSP中所有FGFR（FGFR 1 -4）、其一些配体（FGF 1、2、9）以及作为FGFR 3下游靶点的叉头框N1（FOXN 1）的表达。虽然我们未能检测到FGFR 3的特异性配体FGF 1和FGF 9在DF中的表达，但在DF的表皮区域观察到FGFR 3和FOXN 1的过表达，这表明DF的表皮区域在组织学特征和FGFR 3/FOXN 1的活化方面与脂溢性角化病相似。此外，FGF 2和FGFR 4在DF的肿瘤病变中观察到强表达。FGFR 3/FOXN 1和FGF 2/FGFR 4在DF中的表达模式与DFSP相反。FGFR信号通路的激活不仅与DF的发病机制有关，而且对DF和DFSP的鉴别诊断也有重要意义。
Fibroblast growth factors (FGFs) and their receptors (FGFRs) control a wide range of biological functions; however, their involvement in the pathogenesis of dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) is currently unknown. In this study, we first confirmed the histological diagnosis by detecting fusion COL1A1-PDGFB transcripts in DFSP, and examined the expression of all FGFRs (FGFR1-4), some of their ligands (FGF1, 2, 9), and forkhead box N1 (FOXN1) as a downstream target of FGFR3 in DF and DFSP by immunohistochemical analysis. Although we failed to detect the expression of FGF1 and FGF9 as specific ligands for FGFR3 in DF, overexpression of FGFR3 and FOXN1 was observed in the epidermal regions of DF, suggesting that the epidermal regions of DF were similar to seborrhoeic keratosis both in terms of histological features and the activation of FGFR3/FOXN1. In addition, strong expression of FGF2 and FGFR4 was observed in the tumor lesions of DF. Expression patterns of FGFR3/FOXN1 and FGF2/FGFR4 in DF were in contrast with those of DFSP. The activation of FGFR signaling pathways may be not only relevant to the pathogenesis of DF, but also very useful in the differential diagnosis of DF and DFSP.