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.