Epidermal growth factor receptor signalling contributes to osteoblastic stromal cell proliferation, osteoclastogenesis and disease progression in giant cell tumour of bone.
OBJECTIVE
Epidermal growth factor receptor (EGFR) is implicated in bone remodelling. The aim was to determine whether EGFR protein expression contributes to the aggressiveness and recurrence potential of giant cell tumour of bone (GCTB), an osteolytic primary bone tumour that can exhibit markedly variable clinical behaviour.


RESULTS
Immunohistochemical analysis on tissue microarrays (TMA) of 231 primary, 97 recurrent, 17 metastatic and 26 malignant GCTBs was performed using TMA analysis software and whole digital slides allowing validated scoring. EGFR expression was restricted to neoplastic stromal cells and was significantly more frequent in recurrent (71 of 92; 77%) than in non-recurrent GCTBs (86 of 162; 53%) (P = 0.002); and in clinicoradiologically aggressive (31 of 43; 72%) than latent (27 of 54; 50%) cases (P = 0.034). Detecting phosphotyrosine epitopes pY1068 and -pY1173 indicated active EGFR signalling, and finding EGFR ligands EGF and transforming growth factor-α restricted to cells of the monocytic lineage suggested paracrine EGFR activation in stromal cells. In functional studies EGF supported proliferation of GCTB stromal cells, and the addition of EGF and macrophage-colony stimulating factor promoted osteoclastogenesis.


CONCLUSIONS
In GCTB, EGFR signalling in neoplastic stromal cells may contribute to disease progression through promoting stromal cell proliferation and osteoclastogenesis.
Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
Peter
P
Balla
Linda
L
Moskovszky
Zoltan
Z
Sapi
Ramses
R
Forsyth
Helen
H
Knowles
Nick A
NA
Athanasou
Miklos
M
Szendroi
Laszlo
L
Kopper
Hajnalka
H
Rajnai
Ferenc
F
Pinter
Istvan
I
Petak
Maria Serena
MS
Benassi
Piero
P
Picci
Amalia
A
Conti
Tibor
T
Krenacs
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001862:Bone Resorption / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018212:Giant Cell Tumor of Bone / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
D014408:Biomarkers, Tumor; D066246:ErbB Receptors