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CD56 Expression in Bone and Osteoblastic Neoplasia: A Novel Osteoblast Marker?

CD56 Expression in Bone and Osteoblastic Neoplasia: A Novel Osteoblast Marker?. D.E. Hughes, R. Deb, D.C.Mangham, V.P. Sumathi and R.J. Grimer Royal Orthopaedic Hospital, Birmingham, U.K. CD56/NCAM. Cell adhesion molecule of the immunoglobulin superfamily

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CD56 Expression in Bone and Osteoblastic Neoplasia: A Novel Osteoblast Marker?

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  1. CD56 Expression in Bone and Osteoblastic Neoplasia:A Novel Osteoblast Marker? D.E. Hughes, R. Deb, D.C.Mangham, V.P. Sumathi and R.J. Grimer Royal Orthopaedic Hospital, Birmingham, U.K.

  2. CD56/NCAM • Cell adhesion molecule of the immunoglobulin superfamily • Involved in homotypic cell-cell interactions • Possible role in neural morphogenesis • Restricted tissue distribution

  3. CD56 expression in normal tissues • Neurons, gangliocytes • Plasma cells • Natural killer cells

  4. CD56 expression in tumours • Myeloma • Neuroendocrine carcinomas • Neuroblastoma • Phaeochromocytoma • Some glial tumours • NK-type LGL

  5. Previous evidence of CD56 expression in osteoblast lineage • Expressed by calvarial cells in vitro • Described in association with CD56 expression in myeloma in osteoblasts • Reported in osteosarcomas • Not expressed in Ewing’s sarcoma • Not expressed in chondrosarcoma

  6. Aim of study • To assess CD56 expression in normal cells of the osteoblast lineage • To assess CD56 expression in tumour-like lesions in which bone is formed • To assess CD56 expression in osteoblastic neoplasms

  7. Methods • Cases selected from Royal Orthopaedic Hospital paraffin archive to represent a broad range of normal bone, reactive conditions, tumour-like conditions and osteoblastic tumours • CD56 expression assessed by a standard immunohistochemical approach

  8. Appendix CD56 staining of neural cells Immunohistochemistry • Novacastra anti- CD56 clone 1B6 at 1:50 • High temperature antigen retrieval in citrate/EDTA • Detection by Enivision system

  9. Case selection – benign • Normal/reactive bone (31 cases) • Quiescent bone • Callus, periosteal reaction • Benign bone tumours and tumour-like conditions (24 cases) • Aneurysmal bone cyst • Fibrous dysplasia • Osteofibrous dysplasia • Non-ossifying fibroma • Desmoplastic fibroma • Osteoid osteoma • Osteoblastoma • Giant cell tumour

  10. Case selection – malignant • Malignant osteogenic tumours (23 cases) • High grade intramedullary osteosarcoma • Telangiectatic osteosarcoma • Intermediate grade chondroblastic osteosarcoma • Parosteal osteosarcoma • Low grade central osteosarcoma • Undifferentiated recurrences of known osteosarcomas • Non bone-forming intra-osseous sarcomas

  11. Results: normal bone (1) Strong expression in lining cells and osteoblasts

  12. Weak expression in stromal cells adjacent to osteoblast seams Osteocytes Predominantly negative Results: normal bone (2)

  13. No expression in cartilage No expression in fibroblasts Strong expression in osteoblasts Results: callus

  14. No expression in outer fibrous layer Strong expression in bone-forming areas Results: periosteal reaction

  15. Strong expression on Surface layer of septal structures Background stromal Population negative Results: aneurysmal bone cyst

  16. Results: fibrous dysplasia Spindle cell component positive – most strongly adjacent to areas of bone formation Similar results in osteofibrous dysplasia

  17. Results: non-ossifying fibroma Some expression in spindle cells adjacent to bone Similar results in desmoplastic fibroma

  18. Results: osteoid osteoma Nidus osteoblasts positive Similar results in osteoblastoma

  19. Focal weak expression by spindle cell component Osteoclasts negative Results: giant cell tumour

  20. Most tumour cells positive Strong expression in osteoblastic areas Loss of expression in chondroblastic areas Results: high grade osteosarcoma

  21. Results: parosteal osteosarcoma Variable expression in spindle cell component – stronger adjacent to areas of osteoid Similar results in low grade central osteosarcoma

  22. Focal expression In undifferentiated Tumour cells Results: telangiectatic osteosarcoma

  23. Areas of expression in the absence of osteoid formation Results: undifferentiated recurrence of high grade osteosarcoma Similar results in some undifferentiated intra-osseous sarcomas

  24. Results - summary by cell type: non-neoplastic • Normal osteoblasts – always positive • Normal osteocytes – mostly negative • Normal periosteal spindle cells – positive in areas of active bone formation • Normal bone marrow stromal cells - positive in areas of active bone formation

  25. Results - summary by cell type: neoplastic • Neoplastic osteoblasts – consistently positive • Neoplastic osteocytes – variably positive • Neoplastic spindle cells with osteogenic potential – variably positive • Neoplastic spindle cells without evidence of osteogenic potential – sometimes positive

  26. Conclusions • CD56 is consistently strongly expressed by normal and neoplastic osteoblasts • CD56 expression also occurs in non-osteogenic spindle cells in bone and bone lesions – it may not be a specific marker of osteoblastic potential for diagnostic purposes • CD56 may be a biologically important molecule in osteoblast function

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