Subintimal Ki-67 as a synovial tissue biomarker for inflammatory arthropathies
Subintimal Ki-67 as a synovial tissue biomarker for inflammatory arthropathies
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DOI：
10.1136/ard.2007.071670
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发表时间：
2008-02-01
影响因子：
27.4
通讯作者：
Schumacher, H. R.
中科院分区：
文献类型：
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作者：
Pessler, F.;Ogdie, A.;Schumacher, H. R.
目的：Ki-67表达于分裂细胞的细胞核，可用于评估滑膜炎性细胞和基质细胞的增殖。我们评估了内膜下Ki-67+细胞密度作为炎性关节病的组织生物标志物，并将其与内膜下CD 68（RA的滑膜生物标志物）进行比较。方法：免疫组化法测定了从类风湿关节炎患者滑膜标本中获得的内膜下Ki-67+和CD 68+细胞密度RA（n = 19）、骨关节炎（OA; n = 18）、“非炎性”骨科关节病（缺血性坏死、半月板损伤、股骨骨折; n = 16）、慢性脓毒性关节炎（n = 9）和组织学正常滑膜（n = 10）。结果与组织学滑膜炎评分相关。结果：Ki-67广泛表达于炎性标本内膜下及RA血管翳浸润的硬组织中。与正常对照相比，它在RA（26.6倍）和慢性脓毒性关节炎（55倍）中高度过表达，在OA（3.9倍）和骨科关节病（2.1倍）中轻度升高。Ki-67和CD 68在RA和OA之间的分化相似（AUC：Ki-67 = 0.91，CD 68 = 0.94），Ki-67在慢性脓毒性关节炎和RA之间更好，而CD 68在OA和正常对照之间更好。Ki-67（r = 0.80）和CD-68（r = 0.79）与滑膜炎评分呈正相关。结论：内膜下Ki-67在炎性关节病中过表达，在不同的炎性关节病中有区别，并与滑膜炎的组织学严重程度呈正相关。它可能被证明是有用的滑膜组织分类，并作为一个滑膜标志物的疾病活动在临床试验时，活检是可用的。
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.