Translocation and expression of CSF1 in pigmented villonodular synovitis, tenosynovial giant cell tumor, rheumatoid arthritis and other reactive synovitides.
We recently demonstrated that CSF1, the ligand of the tyrosine kinase receptor, CSF1R, can be translocated in pigmented villonodular synovitis (PVNS) and tenosynovial giant cell tumor (TGCT). In this study, we evaluated the staining characteristics of PVNS/TGCT and reactive synovitides for CSF1 and CSF1R by in situ hybridization and immunohistochemistry on tissue microarrays and correlated these findings with the recently described translocation. We collected specimens of TGCT/PVNS from 60 patients and of rheumatoid arthritis and other reactive synovitides from 74 patients. We identify 2 groups of PVNS and TGCT cases by the presence of CSF1 translocation and CSF1 expression. The first group (35 of 57 cases; 61%) had both the CSF1 translocation and high expression of CSF1 RNA, confirming our previous findings. Interestingly, a second group (22 of 57 cases; 39%) was identified that showed high expression of CSF1 RNA or CSF1 protein but did not have the translocation. The rheumatoid arthritis and reactive synovitis specimens showed localization of CSF1 RNA and protein to the synovial lining cells, implying a possible role for CSF1 in the pathogenesis of these lesions. As the CSF1 translocation is postulated to play an important role in the biology of PVNS/TGCT, the consistent presence of CSF1 expression in translocation-negative cases implies that other mechanisms can lead to CSF1 up-regulation. The consistent presence of CSF1 overexpression in all cases of PVNS/TGCT and reactive synovitides suggests both an important role for CSF1 in the spectrum of synovial pathologies and the possibility of targeting the CSF1/CSF1R interaction therapeutically.
Cupp
John S
JS
Department of Pathology, Stanford University Medical Center, Stanford, CA 94305, USA.
Miller
Melinda A
MA
Montgomery
Kelli D
KD
Nielsen
Torsten O
TO
O'Connell
John X
JX
Huntsman
David
D
van de Rijn
Matt
M
Gilks
Cyril B
CB
West
Robert B
RB
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D003937:Diagnosis, Differential; D005260:Female; D005870:Giant Cell Tumors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D013585:Synovitis / Q000235:genetics* / Q000378:metabolism*; D013586:Synovitis, Pigmented Villonodular / Q000235:genetics / Q000378:metabolism; D046888:Tissue Array Analysis; D014178:Translocation, Genetic
D015415:Biomarkers; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor