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CD56 Expression in Bone and CD56 Expression in Bone and Osteoblastic Neoplasia:Osteoblastic Neoplasia:
A Novel Osteoblast Marker?A Novel Osteoblast Marker?
CD56 Expression in Bone and CD56 Expression in Bone and Osteoblastic Neoplasia:Osteoblastic Neoplasia:
A Novel Osteoblast Marker?A Novel Osteoblast Marker?
D.E. Hughes, R. Deb, D.C.Mangham, V.P. D.E. Hughes, R. Deb, D.C.Mangham, V.P. Sumathi and R.J. GrimerSumathi and R.J. Grimer
Royal Orthopaedic Hospital, Birmingham, Royal Orthopaedic Hospital, Birmingham, U.K.U.K.
D.E. Hughes, R. Deb, D.C.Mangham, V.P. D.E. Hughes, R. Deb, D.C.Mangham, V.P. Sumathi and R.J. GrimerSumathi and R.J. Grimer
Royal Orthopaedic Hospital, Birmingham, Royal Orthopaedic Hospital, Birmingham, U.K.U.K.
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CD56/NCAMCD56/NCAMCD56/NCAMCD56/NCAMCell adhesion molecule of the Cell adhesion molecule of the
immunoglobulin superfamilyimmunoglobulin superfamilyInvolved in homotypic cell-cell Involved in homotypic cell-cell
interactionsinteractionsPossible role in neural morphogenesisPossible role in neural morphogenesisRestricted tissue distributionRestricted tissue distribution
Cell adhesion molecule of the Cell adhesion molecule of the immunoglobulin superfamilyimmunoglobulin superfamily
Involved in homotypic cell-cell Involved in homotypic cell-cell interactionsinteractions
Possible role in neural morphogenesisPossible role in neural morphogenesisRestricted tissue distributionRestricted tissue distribution
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CD56 expression in normal CD56 expression in normal tissuestissues
CD56 expression in normal CD56 expression in normal tissuestissues
Neurons, gangliocytesNeurons, gangliocytesPlasma cellsPlasma cellsNatural killer cellsNatural killer cells
Neurons, gangliocytesNeurons, gangliocytesPlasma cellsPlasma cellsNatural killer cellsNatural killer cells
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CD56 expression in tumoursCD56 expression in tumoursCD56 expression in tumoursCD56 expression in tumours
MyelomaMyelomaNeuroendocrine carcinomasNeuroendocrine carcinomasNeuroblastomaNeuroblastomaPhaeochromocytomaPhaeochromocytomaSome glial tumoursSome glial tumoursNK-type LGLNK-type LGL
MyelomaMyelomaNeuroendocrine carcinomasNeuroendocrine carcinomasNeuroblastomaNeuroblastomaPhaeochromocytomaPhaeochromocytomaSome glial tumoursSome glial tumoursNK-type LGLNK-type LGL
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Previous evidence of CD56 Previous evidence of CD56 expression in osteoblast expression in osteoblast
lineagelineage
Previous evidence of CD56 Previous evidence of CD56 expression in osteoblast expression in osteoblast
lineagelineage
Expressed by calvarial cells in vitroExpressed by calvarial cells in vitroDescribed in association with CD56 expression Described in association with CD56 expression
in myeloma in osteoblastsin myeloma in osteoblastsReported in osteosarcomasReported in osteosarcomasNot expressed in Ewing’s sarcomaNot expressed in Ewing’s sarcomaNot expressed in chondrosarcomaNot expressed in chondrosarcoma
Expressed by calvarial cells in vitroExpressed by calvarial cells in vitroDescribed in association with CD56 expression Described in association with CD56 expression
in myeloma in osteoblastsin myeloma in osteoblastsReported in osteosarcomasReported in osteosarcomasNot expressed in Ewing’s sarcomaNot expressed in Ewing’s sarcomaNot expressed in chondrosarcomaNot expressed in chondrosarcoma
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Aim of studyAim of studyAim of studyAim of study
To assess CD56 expression in normal To assess CD56 expression in normal cells of the osteoblast lineagecells of the osteoblast lineage
To assess CD56 expression in tumour-To assess CD56 expression in tumour-like lesions in which bone is formedlike lesions in which bone is formed
To assess CD56 expression in To assess CD56 expression in osteoblastic neoplasmsosteoblastic neoplasms
To assess CD56 expression in normal To assess CD56 expression in normal cells of the osteoblast lineagecells of the osteoblast lineage
To assess CD56 expression in tumour-To assess CD56 expression in tumour-like lesions in which bone is formedlike lesions in which bone is formed
To assess CD56 expression in To assess CD56 expression in osteoblastic neoplasmsosteoblastic neoplasms
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MethodsMethodsMethodsMethods
Cases selected from Royal Orthopaedic Cases selected from Royal Orthopaedic Hospital paraffin archive to represent a Hospital paraffin archive to represent a broad range of normal bone, reactive broad range of normal bone, reactive conditions, tumour-like conditions and conditions, tumour-like conditions and osteoblastic tumoursosteoblastic tumours
CD56 expression assessed by a standard CD56 expression assessed by a standard immunohistochemical approachimmunohistochemical approach
Cases selected from Royal Orthopaedic Cases selected from Royal Orthopaedic Hospital paraffin archive to represent a Hospital paraffin archive to represent a broad range of normal bone, reactive broad range of normal bone, reactive conditions, tumour-like conditions and conditions, tumour-like conditions and osteoblastic tumoursosteoblastic tumours
CD56 expression assessed by a standard CD56 expression assessed by a standard immunohistochemical approachimmunohistochemical approach
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ImmunohistochemistryImmunohistochemistryImmunohistochemistryImmunohistochemistryNovacastra anti- Novacastra anti-
CD56 clone 1B6 at CD56 clone 1B6 at 1:501:50
High temperature High temperature antigen retrieval in antigen retrieval in citrate/EDTAcitrate/EDTA
Detection by Detection by Enivision systemEnivision system
Novacastra anti- Novacastra anti- CD56 clone 1B6 at CD56 clone 1B6 at 1:501:50
High temperature High temperature antigen retrieval in antigen retrieval in citrate/EDTAcitrate/EDTA
Detection by Detection by Enivision systemEnivision system
AppendixAppendix
CD56 stainingCD56 stainingof neural cellsof neural cells
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Case selection – benign Case selection – benign Case selection – benign Case selection – benign Normal/reactive bone (31 cases)Normal/reactive bone (31 cases)
Quiescent boneQuiescent bone Callus, periosteal reactionCallus, periosteal reaction
Benign bone tumours and tumour-like conditions (24 cases)Benign bone tumours and tumour-like conditions (24 cases) Aneurysmal bone cystAneurysmal bone cyst Fibrous dysplasiaFibrous dysplasia Osteofibrous dysplasiaOsteofibrous dysplasia Non-ossifying fibromaNon-ossifying fibroma Desmoplastic fibromaDesmoplastic fibroma Osteoid osteomaOsteoid osteoma OsteoblastomaOsteoblastoma Giant cell tumourGiant cell tumour
Normal/reactive bone (31 cases)Normal/reactive bone (31 cases) Quiescent boneQuiescent bone Callus, periosteal reactionCallus, periosteal reaction
Benign bone tumours and tumour-like conditions (24 cases)Benign bone tumours and tumour-like conditions (24 cases) Aneurysmal bone cystAneurysmal bone cyst Fibrous dysplasiaFibrous dysplasia Osteofibrous dysplasiaOsteofibrous dysplasia Non-ossifying fibromaNon-ossifying fibroma Desmoplastic fibromaDesmoplastic fibroma Osteoid osteomaOsteoid osteoma OsteoblastomaOsteoblastoma Giant cell tumourGiant cell tumour
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Case selection – malignantCase selection – malignantCase selection – malignantCase selection – malignantMalignant osteogenic tumours (23 cases)Malignant osteogenic tumours (23 cases)
High grade intramedullary osteosarcoma High grade intramedullary osteosarcoma Telangiectatic osteosarcomaTelangiectatic osteosarcoma Intermediate grade chondroblastic osteosarcomaIntermediate grade chondroblastic osteosarcoma Parosteal osteosarcomaParosteal osteosarcoma Low grade central osteosarcomaLow grade central osteosarcoma Undifferentiated recurrences of known osteosarcomasUndifferentiated recurrences of known osteosarcomas Non bone-forming intra-osseous sarcomas Non bone-forming intra-osseous sarcomas
Malignant osteogenic tumours (23 cases)Malignant osteogenic tumours (23 cases) High grade intramedullary osteosarcoma High grade intramedullary osteosarcoma Telangiectatic osteosarcomaTelangiectatic osteosarcoma Intermediate grade chondroblastic osteosarcomaIntermediate grade chondroblastic osteosarcoma Parosteal osteosarcomaParosteal osteosarcoma Low grade central osteosarcomaLow grade central osteosarcoma Undifferentiated recurrences of known osteosarcomasUndifferentiated recurrences of known osteosarcomas Non bone-forming intra-osseous sarcomas Non bone-forming intra-osseous sarcomas
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Results: normal bone (1)Results: normal bone (1)Results: normal bone (1)Results: normal bone (1)
Strong expression inStrong expression inlining cells and osteoblastslining cells and osteoblasts
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Results: normal bone (2)Results: normal bone (2)Results: normal bone (2)Results: normal bone (2)
Weak expression inWeak expression instromal cells adjacent stromal cells adjacent to osteoblast seamsto osteoblast seams
Osteocytes Osteocytes PredominantlyPredominantlynegativenegative
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Results: callusResults: callusResults: callusResults: callus
No expressionNo expressionin cartilagein cartilage
No expressionNo expressionin fibroblastsin fibroblasts
Strong expressionStrong expressionin osteoblastsin osteoblasts
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Results: periosteal reactionResults: periosteal reactionResults: periosteal reactionResults: periosteal reaction
No expression in outerfibrous layer
Strong expressionin bone-forming areas
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Results: aneurysmal bone Results: aneurysmal bone cystcyst
Results: aneurysmal bone Results: aneurysmal bone cystcyst
Strong expression onStrong expression onSurface layer of septalSurface layer of septal
structuresstructures
Background stromal Background stromal Population negativePopulation negative
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Results: fibrous dysplasiaResults: fibrous dysplasiaResults: fibrous dysplasiaResults: fibrous dysplasia
Spindle cell component positive – Spindle cell component positive – most strongly adjacent to areas most strongly adjacent to areas
of bone formationof bone formation
Similar results in osteofibrous dysplasiaSimilar results in osteofibrous dysplasia
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Results: non-ossifying Results: non-ossifying fibromafibroma
Results: non-ossifying Results: non-ossifying fibromafibroma
Some expression Some expression in spindle cells in spindle cells adjacent to boneadjacent to bone
Similar results in desmoplastic fibromaSimilar results in desmoplastic fibroma
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Results: osteoid osteomaResults: osteoid osteomaResults: osteoid osteomaResults: osteoid osteoma
Nidus osteoblastsNidus osteoblasts positivepositive
Similar results in osteoblastomaSimilar results in osteoblastoma
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Results: giant cell tumourResults: giant cell tumourResults: giant cell tumourResults: giant cell tumour
Focal weak expressionFocal weak expressionby spindle cell componentby spindle cell component
Osteoclasts negativeOsteoclasts negative
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Results: high grade Results: high grade osteosarcomaosteosarcoma
Results: high grade Results: high grade osteosarcomaosteosarcoma
Most tumour cells positiveMost tumour cells positive Strong expression inStrong expression inosteoblastic areasosteoblastic areas
Loss of expression inLoss of expression inchondroblastic areaschondroblastic areas
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Results: parosteal Results: parosteal osteosarcomaosteosarcoma
Results: parosteal Results: parosteal osteosarcomaosteosarcoma
Variable expression in spindle cellVariable expression in spindle cellcomponent – stronger adjacent to areas of osteoidcomponent – stronger adjacent to areas of osteoid
Similar results in low grade central osteosarcomaSimilar results in low grade central osteosarcoma
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Results: telangiectatic Results: telangiectatic osteosarcomaosteosarcoma
Results: telangiectatic Results: telangiectatic osteosarcomaosteosarcoma
Focal expressionFocal expressionIn undifferentiatedIn undifferentiatedTumour cellsTumour cells
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Results: undifferentiated Results: undifferentiated recurrence of high grade recurrence of high grade
osteosarcomaosteosarcoma
Results: undifferentiated Results: undifferentiated recurrence of high grade recurrence of high grade
osteosarcomaosteosarcoma
Areas of expression in the Areas of expression in the absence of osteoid formationabsence of osteoid formation
Similar results in some undifferentiated Similar results in some undifferentiated intra-osseous sarcomasintra-osseous sarcomas
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Results - summary by cell Results - summary by cell type: non-neoplastictype: non-neoplastic
Results - summary by cell Results - summary by cell type: non-neoplastictype: non-neoplastic
Normal osteoblasts – always positiveNormal osteoblasts – always positiveNormal osteocytes – mostly negativeNormal osteocytes – mostly negativeNormal periosteal spindle cells – positive Normal periosteal spindle cells – positive
in areas of active bone formationin areas of active bone formationNormal bone marrow stromal cells - Normal bone marrow stromal cells -
positive in areas of active bone formationpositive in areas of active bone formation
Normal osteoblasts – always positiveNormal osteoblasts – always positiveNormal osteocytes – mostly negativeNormal osteocytes – mostly negativeNormal periosteal spindle cells – positive Normal periosteal spindle cells – positive
in areas of active bone formationin areas of active bone formationNormal bone marrow stromal cells - Normal bone marrow stromal cells -
positive in areas of active bone formationpositive in areas of active bone formation
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Results - summary by cell type: Results - summary by cell type: neoplasticneoplastic
Results - summary by cell type: Results - summary by cell type: neoplasticneoplastic
Neoplastic osteoblasts – consistently positiveNeoplastic osteoblasts – consistently positive Neoplastic osteocytes – variably positiveNeoplastic osteocytes – variably positive Neoplastic spindle cells with osteogenic Neoplastic spindle cells with osteogenic
potential – variably positivepotential – variably positive Neoplastic spindle cells without evidence of Neoplastic spindle cells without evidence of
osteogenic potential – sometimes positiveosteogenic potential – sometimes positive
Neoplastic osteoblasts – consistently positiveNeoplastic osteoblasts – consistently positive Neoplastic osteocytes – variably positiveNeoplastic osteocytes – variably positive Neoplastic spindle cells with osteogenic Neoplastic spindle cells with osteogenic
potential – variably positivepotential – variably positive Neoplastic spindle cells without evidence of Neoplastic spindle cells without evidence of
osteogenic potential – sometimes positiveosteogenic potential – sometimes positive
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ConclusionsConclusionsConclusionsConclusionsCD56 is consistently strongly expressed CD56 is consistently strongly expressed
by normal and neoplastic osteoblastsby normal and neoplastic osteoblastsCD56 expression also occurs in non-CD56 expression also occurs in non-
osteogenic spindle cells in bone and bone osteogenic spindle cells in bone and bone lesions – lesions – it may not be a specific marker it may not be a specific marker of osteoblastic potential for diagnostic of osteoblastic potential for diagnostic purposespurposes
CD56 may be a biologically important CD56 may be a biologically important molecule in osteoblast functionmolecule in osteoblast function
CD56 is consistently strongly expressed CD56 is consistently strongly expressed by normal and neoplastic osteoblastsby normal and neoplastic osteoblasts
CD56 expression also occurs in non-CD56 expression also occurs in non-osteogenic spindle cells in bone and bone osteogenic spindle cells in bone and bone lesions – lesions – it may not be a specific marker it may not be a specific marker of osteoblastic potential for diagnostic of osteoblastic potential for diagnostic purposespurposes
CD56 may be a biologically important CD56 may be a biologically important molecule in osteoblast functionmolecule in osteoblast function