Parathyroid Hormone-Related Peptide Expression in Cartilaginous Tumors

Department of Orthopaedic Surgery, University of Rochester School of Medicine, Rochester, NY 14642, USA.
Clinical Orthopaedics and Related Research (Impact Factor: 2.77). 11/2002; 403(403):198-204. DOI: 10.1097/00003086-200210000-00029
Source: PubMed


Parathyroid hormone-related peptide is one of the most important regulators of chondrocyte proliferation. Although cartilaginous neoplasms express different collagens, including Types II and X, the pathogenesis of these tumors has not been elucidated. The current study examined the hypothesis that parathyroid hormone-related peptide is expressed in cartilaginous neoplasms and its level of expression may correlate with the proliferative rate of cartilaginous neoplasms with higher levels in more malignant tumors and lower levels in benign lesions. Two hundred thirty-four biopsy and resection specimens of benign and malignant cartilage tumors from 179 patients were retrieved from surgical pathology archival material and analyzed immunohistochemically using an antibody to human parathyroid hormone-related peptide. Most cartilaginous neoplasms had some level of expression of parathyroid hormone-related peptide, and tumors with a more proliferative phenotype had higher levels of parathyroid hormone-related peptide. Although benign lesions such as enchondromas and osteochondromas had low levels of parathyroid hormone-related peptide, malignant neoplasms such as extraskeletal myxoid chondrosarcomas, dedifferentiated chondrosarcomas, and mesenchymal chondrosarcomas expressed high levels of parathyroid hormone-related peptide. Parathyroid hormone-related peptide expression correlated with grade of malignancy in chondrosarcoma. Although there were highly significant differences between Grade I chondrosarcoma versus Grade II and Grade III lesions, the difference between Grade II and Grade III chondrosarcomas approached significance. Parathyroid hormone-related peptide may represent a new tumor marker with potential diagnostic use in classifying cartilaginous neoplasms.

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    • "Little is known about the molecular mechanisms involved in the malignant transformation from enchondromas to chondrosarcomas. Expression of PTHrP, the PTHR1, and their downstream partner Bcl2 may be correlated with the grade of malignancy in chondrosarcoma [16-19]. "
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    ABSTRACT: Enchondromas are common intraosseous, usually benign cartilaginous tumors, that develop in close proximity to growth plate cartilage. When multiple enchondromas are present, the condition is called enchondromatosis also known as Ollier disease (WHO terminology). The estimated prevalence of Ollier disease is 1/100,000. Clinical manifestations often appear in the first decade of life. Ollier disease is characterized by an asymmetric distribution of cartilage lesions and these can be extremely variable (in terms of size, number, location, evolution of enchondromas, age of onset and of diagnosis, requirement for surgery). Clinical problems caused by enchondromas include skeletal deformities, limb-length discrepancy, and the potential risk for malignant change to chondrosarcoma. The condition in which multiple enchondromatosis is associated with soft tissue hemangiomas is known as Maffucci syndrome. Until now both Ollier disease and Maffucci syndrome have only occurred in isolated patients and not familial. It remains uncertain whether the disorder is caused by a single gene defect or by combinations of (germ-line and/or somatic) mutations. The diagnosis is based on clinical and conventional radiological evaluations. Histological analysis has a limited role and is mainly used if malignancy is suspected. There is no medical treatment for enchondromatosis. Surgery is indicated in case of complications (pathological fractures, growth defect, malignant transformation). The prognosis for Ollier disease is difficult to assess. As is generally the case, forms with an early onset appear more severe. Enchondromas in Ollier disease present a risk of malignant transformation of enchondromas into chondrosarcomas.
    Orphanet Journal of Rare Diseases 02/2006; 1(1):37. DOI:10.1186/1750-1172-1-37 · 3.36 Impact Factor
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    ABSTRACT: Osteochondroma is a cartilage capped benign bone tumour, arising at the external surface of bones preformed by endochondral ossification. A small percentage of osteochondromas can progress towards its malignant counterpart, secondary peripheral chondrosarcoma. About 15% of osteochondromas occur in the context of a rare hereditary syndrome, Multiple Osteochondromas for which two genes have been identified as causative genes, namely EXT1 and EXT2, which have been identified as tumor suppressor genes. However the vast majority of osteochondromas present as solitary lesions. We were able to demonstrate that similar to hereditary osteochondromas EXT1 also acts as a classical tumour suppressor gene in solitary osteochondroma. The EXT genes function as a complex in the biosynthesis of heparin sulphate proteoglycans (HSPGs), large multifunctional macromolecules that are involved in several growth signaling pathways. We showed that the loss of EXT1 and in hereditary cases also EXT2 is accompanied by intracellular accumulation of HSPGs, suggesting a disrupted EXT1/2 complex. The growth signalling pathways known from normal longitudinal bone growth are affected differently in osteochondromas and chondrosarcomas. The IHH signaling functions autonomously in osteochondromas and its activity decreases during malignant transformation and progression of chondrosarcomas, whereas the PTHLH and TFG-β signaling cascades seem to be re-activated.
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    ABSTRACT: Proefschrift Universiteit Leiden. Met samenvatting in het Nederlands.
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