Bovée J V M G, Hameetman L, Kroon H M, Aigner T, Hogendoorn P C W
Department of Pathology, Leiden University Medical Centre, The Netherlands.
J Pathol. 2006 Jul;209(3):411-9. doi: 10.1002/path.1985.
Dysplasia epiphysealis hemimelica (DEH) and metachondromatosis (MC) are considered in the differential diagnosis of solitary and hereditary osteochondromas. Both are rare disorders with DEH demonstrating cartilaginous overgrowth of an epiphysis and MC exhibiting synchronous enchondromas and osteochondromas. Ten cases of DEH and two of MC were compared with osteochondromas at the histological and molecular level. Histologically, clumping of chondrocytes within a fibrillary chondroid matrix is characteristic of DEH, while osteochondromas and MC display the characteristic growth plate architecture. Using cDNA microarray analysis we demonstrate that DEH and MC cluster separately from osteochondromas and growth plates. The EXT genes, involved in the hereditary multiple osteochondromas syndrome, and downregulated in osteochondroma, were normally expressed in DEH and MC as shown by quantitative reverse transcriptase-polymerase chain reaction (qPCR). EXT is involved in heparan sulphate biosynthesis, important for Indian Hedgehog/ParaThyroid Hormone Like Hormone (IHH/PTHLH) growth plate signalling pathways. IHH/PTHLH signalling molecules were expressed in DEH and MC as shown by both qPCR and immunohistochemistry, suggesting that this pathway is active. This is in contrast to osteochondroma, in which PTHLH signalling is downregulated. Thus, lesions of DEH and MC are separate entities from osteochondroma as confirmed by their different cDNA and protein expression profiles. Downstream targets of EXT, which are downregulated in osteochondroma, are expressed in DEH and MC, suggesting that EXT signalling is not disturbed.
半侧肢体骨骺发育异常（DEH）和软骨瘤病（MC）被纳入孤立性和遗传性骨软骨瘤的鉴别诊断中。两者均为罕见疾病，DEH表现为骨骺的软骨过度生长，MC则表现为同步的内生软骨瘤和骨软骨瘤。将10例DEH病例和2例MC病例在组织学和分子水平上与骨软骨瘤进行比较。组织学上，DEH的特征是在纤维状软骨样基质内软骨细胞聚集，而骨软骨瘤和MC则显示出特征性的生长板结构。使用cDNA微阵列分析，我们证明DEH和MC与骨软骨瘤和生长板分别聚类。参与遗传性多发性骨软骨瘤综合征且在骨软骨瘤中表达下调的EXT基因，通过定量逆转录-聚合酶链反应（qPCR）显示在DEH和MC中正常表达。EXT参与硫酸乙酰肝素的生物合成，这对印度刺猬/甲状旁腺激素样激素（IHH/PTHLH）生长板信号通路很重要。qPCR和免疫组织化学均显示DEH和MC中表达IHH/PTHLH信号分子，表明该信号通路是活跃的。这与骨软骨瘤相反，在骨软骨瘤中PTHLH信号下调。因此，DEH和MC的病变与骨软骨瘤是不同的实体，这通过它们不同的cDNA和蛋白质表达谱得到证实。在骨软骨瘤中表达下调的EXT下游靶点在DEH和MC中表达，表明EXT信号未受干扰。
