Absence of IHH and retention of PTHrP signalling in enchondromas and central chondrosarcomas

• Published in: The Journal of pathology Vol. 205; no. 4; pp. 476 - 482
• Main Authors: Rozeman, Leida B, Hameetman, Liesbeth, Cleton-Jansen, Anne-Marie, Taminiau, Anthonie HM, Hogendoorn, Pancras CW, Bovée, Judith VMG
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-03-2005; Wiley
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Biological and medical sciences; bone; bone neoplasm; Bone Neoplasms - chemistry; Bone Neoplasms - pathology; Cell Transformation, Neoplastic - pathology; Child; Child, Preschool; chondrosarcoma; Chondrosarcoma - chemistry; Chondrosarcoma - pathology; Diseases of the osteoarticular system; enchondroma; enchondromatosis; Enchondromatosis - metabolism; Enchondromatosis - pathology; Female; Fingers - pathology; Hedgehog Proteins; Humans; Immunohistochemistry - methods; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Middle Aged; Ollier disease; Parathyroid Hormone-Related Protein - analysis; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Polymerase Chain Reaction - methods; RNA, Messenger - analysis; RNA, Neoplasm - analysis; Signal Transduction - physiology; Trans-Activators - analysis; Tumors of striated muscle and skeleton; Chondrosarcoma; Sarcoma; Diseases of the osteoarticular system; Malignant tumor; Enchondroma; Retention; Signalling; Ollier disease; Osteoarticular system; Cartilage; Anatomic pathology; Chondroma; Signaling pathway; enchondromatosis; Parathyroid hormone related peptide; Benign neoplasm; Bone; bone neoplasm
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.1723

Enchondromas and conventional central chondrosarcomas are, respectively, benign and malignant hyaline cartilage‐forming tumours that originate in the medulla of bone. In order to gain a better understanding of the molecular process underlying malignant transformation of enchondroma, and to investigate whether there is a biological difference between conventional central cartilaginous tumours and those of enchondromatosis or with phalangeal localization, a series of 64 enchondromas (phalanx, n = 21; enchondromatosis, n = 15) and 89 chondrosarcomas (phalanx, n = 17; enchondromatosis, n = 13) was collected. Indian Hedgehog (IHH)/parathyroid hormone related peptide (PTHrP) signalling, an important pathway in chondrocyte proliferation and differentiation within the normal growth plate, was studied by immunohistochemical analysis of the expression of PTHrP, PTHR1, Bcl‐2, p21, cyclin D1, and cyclin E. Quantitative real‐time PCR for IHH, PTCH, SMO, and GLI2 was performed on a subset of tumours. The data show that IHH signalling is absent in enchondromas and central chondrosarcomas, while PTHrP signalling is active. There was no difference in the expression of any of the molecules between 35 enchondromas and 26 grade I central chondrosarcomas, indicating that PTHrP signalling is not important in malignant transformation of enchondroma. Higher expression of PTHR1 and Bcl‐2 was associated with increasing histological grade in chondrosarcoma, suggesting involvement in tumour progression. No difference was found between samples from enchondromatosis patients and solitary cases, suggesting no difference in PTHrP signalling. A small subset of phalangeal chondrosarcomas demonstrated down‐regulation of PTHrP, which may be related to its more indolent clinical behaviour. Thus, in both enchondromas and central chondrosarcomas, PTHrP signalling is active and independent of IHH signalling, irrespective of the presence or absence of enchondromatosis. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.