title: Subintimal Ki-67 as a synovial tissue biomarker for inflammatory arthropathies.
abstract: OBJECTIVE
  Ki-67 is expressed in the nuclei of dividing cells and can be used to assess proliferation of synovial inflammatory and stromal cells. We evaluated subintimal Ki-67+ cell density as a tissue biomarker for inflammatory arthropathies and compared it to subintimal CD68, a synovial biomarker of RA.
  
  
  METHODS
  Subintimal Ki-67+ and CD68+ cell densities were measured immunohistochemically in synovial specimens obtained from patients with rheumatoid arthritis (RA; n = 19), osteoarthritis (OA; n = 18), "non-inflammatory" orthopaedic arthropathies (avascular necrosis, meniscus injury, femur fracture; n = 16), chronic septic arthritis (n = 9), and histologically normal synovium (n = 10).
  
  
  RESULTS
  were correlated with a histological synovitis score. Utilising the areas under receiver operating characteristic curves (AUCs), we compared the abilities of Ki-67 and CD68 to differentiate among these arthropathies. Results: Ki-67 was expressed widely in the subintimal of inflamed specimens and in RA pannus invading hard tissues. Compared to normal controls, it was highly overexpressed in RA (26.6-fold) and chronic septic arthritis (55-fold), and mildly elevated in OA (3.9-fold) and orthopaedic arthropathies (2.1-fold). Ki-67 and CD68 differentiated similarly well between RA and OA (AUC: Ki-67 = 0.91, CD68 = 0.94), Ki-67 better between chronic septic arthritis and RA, and CD68 better between OA and normal controls. Ki-67 (r = 0.80) and CD68 (r = 0.79) correlated positively with the synovitis score.
  
  
  CONCLUSIONS
  Subintimal Ki-67 was overexpressed in inflammatory arthropathies, distinguished among differentially inflamed arthropathies, and correlated positively with the histological severity of synovitis. It may prove useful in synovial tissue classification and as a synovial marker of disease activity in clinical trials when biopsies are available.
authors.affiliation: The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. frank.pessler@uniklinikum-dresden.de
authors.forename: F
authors.initials: F
authors.lastname: Pessler
authors.forename: A
authors.initials: A
authors.lastname: Ogdie
authors.forename: C
authors.initials: C
authors.lastname: Diaz-Torne
authors.forename: L
authors.initials: L
authors.lastname: Dai
authors.forename: X
authors.initials: X
authors.lastname: Yu
authors.forename: E
authors.initials: E
authors.lastname: Einhorn
authors.forename: S
authors.initials: S
authors.lastname: Gay
authors.forename: H R
authors.initials: HR
authors.lastname: Schumacher
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology*; D002452:Cell Count / Q000379:methods; D002455:Cell Division; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D007719:Knee Joint / Q000276:immunology / Q000473:pathology; D008297:Male; D012372:ROC Curve; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology; D013585:Synovitis / Q000276:immunology / Q000473:pathology*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D019394:Ki-67 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule