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The use of Bcl-2 and PTHLH immunohistochemistry in the diagnosis of peripheral chondrosarcoma in a clinicopathological setting

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Abstract

Distinguishing osteochondroma from low-grade secondary peripheral chondrosarcoma can be difficult. In osteochondroma, growth-signalling pathways are thought to be downregulated through exostosin (EXT) inactivation. A previous pilot study focusing on expression of putative EXT downstream effectors indicated that progression of osteochondroma towards grade I chondrosarcoma was characterised by upregulation of Bcl-2 and parathyroid hormone-like hormone (PTHLH). We investigated their use as diagnostic markers in a large nationwide series of 71 osteochondromas and 34 chondrosarcomas. Bcl-2 immunohistochemistry proved to be a valuable diagnostic tool: scoring negative in 95% (specificity) of the osteochondromas and positive in 57% (sensitivity) of the chondrosarcomas, reaching a positive predictive value of 84% and negative predictive value of 82%. Positivity was not related to age, hereditary status, gender or thickness of the cartilage cap. Presence of internal controls and verification using mRNA in situ hybridisation strengthened the reliability of the immunohistochemical staining. PTHLH showed more variable staining, being positive in osteochondromas from females or adolescent males, suggesting age- and gender-dependent expression. Thus, in cases where the distinction between osteochondroma and chondrosarcoma is difficult, Bcl-2 is a valuable diagnostic marker for malignancy, regardless of tumour size, patient gender or age, and this can be extended with PTHLH for non-adolescent male patients.

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Acknowledgements

The contribution of the Dutch national pathology database ‘Stichting PALGA’ and the Netherlands Committee of Bone Tumours to this study is thankfully acknowledged. The authors gratefully acknowledge Hans J. Baelde and Ayse Yavas for expert technical assistance, Dr. M. Karperien for fruitful discussions, Klaas G. van der Ham for graphical assistance and the different medical centres that shared their cases with us. This work was financially supported by the Dutch Cancer Society (grant-no. RUL 2002–2738) and was presented in part at the 91st annual meeting of the United States and Canadian Academy of Pathology (USCAP, 2002) and the 15th annual meeting of the European Musculoskeletal Oncology Society (EMSOS, 2002). All investigations were performed according to the national ethics guidelines for the use of patient material.

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Authors and Affiliations

  1. Department of Pathology, Leiden University Medical Centre, L1-Q, PO Box 9600, 2300 RC, Leiden, The Netherlands

    Liesbeth Hameetman, Petra Kok, Anne-Marie Cleton-Jansen, Pancras C. W. Hogendoorn & Judith V. M. G. Bovée

  2. Department of Medical Statistics, Leiden University Medical Centre, Leiden, The Netherlands

    Paul H. C. Eilers

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  1. Liesbeth Hameetman
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  2. Petra Kok
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  3. Paul H. C. Eilers
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  5. Pancras C. W. Hogendoorn
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  6. Judith V. M. G. Bovée
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Correspondence to Judith V. M. G. Bovée.

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Hameetman, L., Kok, P., Eilers, P.H.C. et al. The use of Bcl-2 and PTHLH immunohistochemistry in the diagnosis of peripheral chondrosarcoma in a clinicopathological setting. Virchows Arch 446, 430–437 (2005). https://doi.org/10.1007/s00428-005-1208-4

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  • DOI: https://doi.org/10.1007/s00428-005-1208-4

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