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(American Journal of Pathology. 2000;157:1587-1595.)
© 2000 American Society for Investigative Pathology

Regular Articles

Near-Haploidy and Subsequent Polyploidization Characterize the Progression of Peripheral Chondrosarcoma

Judith V. M. G. Bovée^*, Martin van Royen^*, Alfons F. J. Bardoel, Carla Rosenberg^§, Cees J. Cornelisse^*, Anne-Marie Cleton-Jansen^* and Pancras C. W. Hogendoorn^*

From the Department of Pathology^*
and the Department of Molecular Cell Biology,
Laboratory of Cytochemistry and Cytometry, Leiden University Medical Center, Leiden; the Department of Medical Genetics,
Utrecht University Medical Center, Utrecht; and the Laboratory for Experimental Patho-Oncology,^§
Daniel den Hoed Cancer Center, University Hospital Rotterdam, Rotterdam, The Netherlands

Chondrosarcomas are malignant cartilaginous tumors arising centrally in bone (central chondrosarcoma), or secondarily within the cartilaginous cap of osteochondroma (peripheral chondrosarcoma). We previously used DNA flow cytometry to demonstrate that near-haploidy is relatively frequent in peripheral chondrosarcomas. We performed fluorescence in situ hybridization (FISH) to interphase nuclei using centromeric probes, a genome wide loss of heterozygosity (LOH) analysis, and comparative genomic hybridization on five peripheral chondrosarcomas. We demonstrated near-haploidy in two low-grade tumors with only one copy and LOH of most chromosomes. Few chromosomes are disomic, with retention of heterozygosity and overrepresentation at comparative genomic hybridization. One tumor contains both a near-haploid clone with chromosomes in monosomic and disomic state, and an exactly duplicated clone. Two high-grade tumors clearly demonstrate polyploidization because most chromosomes show LOH and two copies at FISH, whereas few chromosomes have four copies with retention of heterozygosity. Using DNA from a relative, we demonstrate that chromosome loss is random regardless of parental origin. Using FISH on paraffin slides, we exclude near-haploidy to result from meiosis-like division in binucleated cells, characteristic for chondrosarcoma. In conclusion, our results indicate that near-haploidy characterizes the progression from osteochondroma toward low-grade chondrosarcoma. Moreover, further progression toward high-grade chondrosarcoma is characterized by polyploidization.

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