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Subintimal Ki-67 as a synovial tissue biomarker for inflammatory arthropathies
  1. F Pessler1,
  2. A Ogdie2,
  3. C Diaz-Torne3,
  4. L Dai3,
  5. X Yu2,
  6. E Einhorn4,
  7. S Gay5,
  8. H R Schumacher3
  1. 1
    The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
  2. 2
    University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
  3. 3
    University of Pennsylvania School of Medicine, Division of Rheumatology, Philadelphia, Pennsylvania, USA
  4. 4
    Department of Pathology, Philadelphia VA Medical Center, Philadelphia, Pennsylvania, USA
  5. 5
    WHO Collaborating Center for Molecular Biology and Novel Therapeutic Strategies for Rheumatic Diseases, University of Zürich, Switzerland
  1. F Pessler, Klinik und Poliklinik für Kinder- und Jugendmedizin, Technische Universität Dresden, Dresden, Germany; frank.pessler{at}


Objectives: 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 subintima 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.

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  • Funding: FP was supported by National Institutes of Health Training Grants T32-AR 007442 and T32-CA 09140.

  • Competing interests: None.