p53 overexpression in synovial tissue from patients with early and longstanding rheumatoid arthritis compared with patients with reactive arthritis and osteoarthritis

Objective. The p53 tumor suppressor gene is overexpressed in synovial tissu e (ST) from patients with longstanding rheumatoid arthritis (RA), and may c ontain somatic mutations. The aim of this study was to determine p53 expres sion in ST from RA patients in different stages of the disease, compared wi th disease controls. Methods. ST biopsy specimens were obtained from the knee joints of 31 RA pa tients in varying disease phases, 8 patients with reactive arthritis (ReA), 10 patients with inflammatory osteoarthritis (OA), and 6 control patients (4 with meniscus pathology, 2 with vascular insufficiency). ST was also obt ained from the clinically uninvolved knee joints of 9 RA patients, Expressi on of p53 was determined by immunohistology with DO1 monoclonal antibody (m Ab) in all patients and by Western blot analysis with DO7 mAb in a subgroup of the patients. Results. The p53 protein was detected by immunohistology in 10 of the 13 pa tients with early RA (duration <6 months) and in 12 of the 14 patients with longstanding RA (duration >5 years), The p53 protein was also demonstrated in clinically uninvolved knee joints. Western blots revealed immunoreactiv e p53 in ST extracts from all RA patients. Expression of p53 was about twic e as high in ST from patients,vith longstanding RA as in early RA samples, but the difference did not reach statistical significance. Small amounts of p53 were also detected in ST from ReA and OA patients, although the expres sion in RA synovium was significantly higher. Immunohistologic analysis of normal ST gave negative results for p53. Conclusion. This study shows that p53 overexpression is specific for RA, co mpared with OA and ReA, This phenomenon is probably secondary to increased production of wild-type p53 protein in response to DNA damage and secondary to somatic mutations caused by the genotoxic local environment in inflamed ST. Of interest, p53 overexpression can also be found in the earliest stag es of RA and in clinically uninvolved joints.