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Subintimal Ki-67 as a synovial tissue biomarker for inflammatory arthropathies
  1. F Pessler (pessler{at}email.chop.edu)
  1. Children's Hospital of Philadelphia, United States
    1. A Ogdie (alexis.ogdie{at}uphs.upenn.edu)
    1. University of Pennsylvania, United States
      1. C Diaz-Torne (cesardiaztorne{at}gmail.com)
      1. Hospital Universitari de Bellvitge, Barcelona, Spain
        1. L Dai (liedai2004{at}hotmail.com)
        1. 2nd Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
          1. X Yu (glxiaoxia{at}126.com)
          1. Traditional Chinese Medicine-Western Medicine Hospital, Cangzhou of Hebei, China
            1. E Einhorn (eugene.einhorn{at}va.gov)
            1. Philadelphia VA Medical Center, Dept. of Pathology, United States
              1. S Gay (steffen.gay{at}usz.ch)
              1. WHO Center for Molecular Biology and Novel Therapeutic Strategies for Rheumatic Diseases,, Switzerland
                1. H R Schumacher (schumacr{at}mail.med.upenn.edu)
                1. Philadelphia VA Medical Center, United States

                  Abstract

                  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” orthopedic 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 histologic synovitis score. Utilizing 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 orthopedic 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 over-expressed in inflammatory arthropathies, distinguished among differentially inflamed arthropathies, and correlated positively with the histologic 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.

                  • CD68
                  • Ki-67
                  • rheumatoid arthritis
                  • septic arthritis
                  • synovium

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