EXT-related pathways are not involved in the pathogenesis of dysplasia epiphysealis hemimelica and metachondromatosis

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 osteocho...

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Bibliographic Details
Published in:The Journal of pathology 2006-07, Vol.209 (3), p.411-419
Main Authors: Bovée, JVMG, Hameetman, L, Kroon, HM, Aigner, T, Hogendoorn, PCW
Format: Article
Language:English
Subjects:
Adolescent
Adult
Biological and medical sciences
Bone Neoplasms - diagnosis
Bone Neoplasms - genetics
Bone Neoplasms - physiopathology
bone tumours
Child
Child, Preschool
chondrocytes
Diagnosis, Differential
DNA, Complementary - genetics
Exostoses, Multiple Hereditary - diagnosis
Exostoses, Multiple Hereditary - genetics
Exostoses, Multiple Hereditary - physiopathology
Female
gene expression
Gene Expression Regulation
Gene Expression Regulation, Neoplastic
growth factors
Humans
Investigative techniques, diagnostic techniques (general aspects)
Male
Medical sciences
N-Acetylglucosaminyltransferases - genetics
N-Acetylglucosaminyltransferases - physiology
Neoplasm Proteins - genetics
Neoplasm Proteins - physiology
Oligonucleotide Array Sequence Analysis - methods
Osteochondrodysplasias - diagnosis
Osteochondrodysplasias - genetics
Osteochondrodysplasias - physiopathology
Osteochondroma - diagnosis
Osteochondroma - genetics
Osteochondroma - physiopathology
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
Polymerase Chain Reaction - methods
PTHLH and PTHR1
Signal Transduction
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Summary: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. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
ISSN:0022-3417
1096-9896
DOI:10.1002/path.1985