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Subintimal Ki-67 as a synovial tissue biomarker for inflammatory arthropathies


Pessler, F; Ogdie, A; Diaz-Torne, C; Dai, L; Yu, X; Einhorn, E; Gay, S; Schumacher, H R (2008). Subintimal Ki-67 as a synovial tissue biomarker for inflammatory arthropathies. Annals of the Rheumatic Diseases, 67(2):162-167.

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" 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.

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 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2008
Deposited On:05 Aug 2008 10:19
Last Modified:05 Apr 2016 12:25
Publisher:BMJ Publishing Group
ISSN:0003-4967
Publisher DOI:10.1136/ard.2007.071670
PubMed ID:17613556
Permanent URL: http://doi.org/10.5167/uzh-2875

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