真皮纤维瘤和隆突性皮肤纤维肉瘤分子表型差异及组织起源探讨

Differences of the molecular phenotypes and the histogenesis between dermatofibroma and dermatofibrosarcoma protuberans

目的:探讨真皮纤维瘤(dermatofibroma,DF)和隆突性皮肤纤维肉瘤(dermatofibrosarcoma protuberans,DFSP)的组织起源和分化。方法:选取DF和DFSP各26例,收集详细临床资料,分析两组的组织病理形态;采用组织芯片对全部病例进行免疫组织化学染色分析,抗体为Factor ⅩⅢa,HLA-DR,CD34,CD14,S-100,MSA和Ki67;用体外转录法制备转化生长因子(transforming growth factor β,TGF-β)和碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)探针;用原位杂交法检测TGF-β和bFGF在肿瘤中的表达。结果:全部病例均不同程度表达FactorⅩⅢa,HLA-DR和CD34。三者阳性细胞率的中位数在26例DF中分别为:FactorⅩⅢa为90%,HLA-DR为70%,CD34为5%。三者阳性细胞率的中位数在26例DFSP中分别为:FactorⅩⅢa为10%,HLA-DR为5%,CD34为80%。3例DF和1例DFSP有少数细胞CD14阳性。2例DF和6例DFSP有少数细胞S-100阳性。3例DF和5例DFSP有极少数细胞MSA阳性。全部病例Ki67阳性细胞率小于5%。原位杂交检测结果:TGF-β在DF中的表达强度高于DFSP。结论:DF和DFSP不同程度表达树突状细胞(dendritic cell,DC)谱系特征,DF在组织形态和免疫表型上更趋向表达成熟DC特征,支持该肿瘤良性的生物学行为;而DFSP趋向显示不成熟的真皮储备细胞(dermal reserve cell,DRC)特征,与该肿瘤低度恶性生物学行为相符;某些肿瘤两种抗体表达的阳性细胞率呈中间状态;有关FactorⅩⅢa和CD34表达差异的认识和运用有助于肿瘤的诊断和鉴别诊断。

Objective：To explore the histogenesis and differentiation of dermatofibroma （DF） and dermatofibrosarcoma protuberans （DFSP）. Methods： Clinical information and microscopic characteristics of 26 cases of DF and 26 cases of DFSP were investigated. The immunohistochemical study was performed on microarray sections by a panel of antibodies including FactorⅫa, HLA-DR, CD34, CD14, S-100, MSA, and Ki67. Probe was labeled by in vitro transcription. The mRNA expression levels of TGF-β and bFGF were investigated by in situ hybridization. Results： All cases showed positive for Factor Ⅻa, HLA- DR and CD34 to different extent. The medians of positive rates in DF were FactorⅫa 90% , HLA-DR 70% , and CD34 5% , and in DFSP were FactorⅫa 10% , HLA-DR 5% , and CD34 80%. CD14 was positive in 3 cases of DF and 1 case of DFSP. S-100 was positive in 6 cases of DFSP and 2 cases of DF. MSA was positive in 5 cases of DFSP and 3 cases of DF. In all cases, positive rate of Ki67 was less than 5%. The mRNA expression levels of TGF-β was elevated in DF in comparison with DFSP. Conclusion： Both DF and DFSP can differentiate to dendritic cells （DC） in different degree. Considering the character of microscopic features and immunohistochemical phenotype, cells of DF are much similar to mature DC, while those of DFSP much similar to immature dermal reserve cell （DRC）. The differences of cell differentiation between DF and DFSP result in different prognosis. DF is a benign tumor, while DFSP a low grade malignant tumor. The different expression of FactorⅫa and CD34 may be helpful to differential diagnosis of DF and DFSP.