title: Malignant progression in multiple enchondromatosis (Ollier's disease): an autopsy-based molecular genetic study.
abstract: Multiple enchondromatosis (Ollier's disease) is a nonhereditary disease characterized by multiple central (medullary) cartilaginous bone tumors of unknown pathogenesis. It usually involves the extremities with a unilateral predominance, and sarcomatous transformation may occur. We report an autopsy-based genetic study of a 34-year-old man presenting in early adolescence with multiple enchondromas of the extremities, predominantly left-sided, compatible with Ollier's disease. Twelve years after presentation, malignant transformation to a high grade chondrosarcoma occurred in a tibial enchondroma. The patient died after widespread metastatic disease. Loss of heterozygosity (LOH), in the tibial chondrosarcoma and its metastases, was identified exclusively on chromosome bands 13q14 and 9p21, while being absent in the femoral enchondroma analyzed. Similarly, p53 overexpression was identified immunohistochemically in the tibial chondrosarcoma and its metastases, while being absent in the femoral enchondroma; LOH at 17p13 however, was not demonstrable. It is hypothesized that inactivation of putative tumor suppressor genes at 9p21 and 13q14, and overexpression of p53, identified in the chondrosarcoma and its metastases, but absent in enchondroma, may be related to sarcomatous transformation in Ollier's disease.
authors.affiliation: Department of Pathology, Leiden University Medical Center, The Netherlands.
authors.forename: J V
authors.initials: JV
authors.lastname: Bovée
authors.forename: J F
authors.initials: JF
authors.lastname: van Roggen
authors.forename: A M
authors.initials: AM
authors.lastname: Cleton-Jansen
authors.forename: A H
authors.initials: AH
authors.lastname: Taminiau
authors.forename: H J
authors.initials: HJ
authors.lastname: van der Woude
authors.forename: P C
authors.initials: PC
authors.lastname: Hogendoorn
mesh_terms: D000328:Adult; D001344:Autopsy; D001932:Brain Neoplasms / Q000556:secondary; D002813:Chondrosarcoma / Q000556:secondary; D002882:Chromosomes, Human, Pair 13; D002899:Chromosomes, Human, Pair 9; D004687:Enchondromatosis / Q000235:genetics / Q000473:pathology*; D017809:Fatal Outcome; D005434:Flow Cytometry; D007839:Functional Laterality; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D009362:Neoplasm Metastasis; D018807:Polymorphism, Single-Stranded Conformational