Expression of tyrosine kinase receptors Tie-1 and Tie-2 in giant cell tumor of the tendon sheath: A possible role in synovial proliferation

We have recently demonstrated that Tie-1 and Tie-2 are expressed in synovia l cells from rheumatoid arthritis (RA). To elucidate the possible involveme nt of Tie receptors in synovial proliferation, we analyzed their expression by immunostaining in five cases of giant cell tumor of tendon sheath (GCTT S), which represents a proliferating lesion of synovial cells. Strong immun oreactivity for both Tie-1 and Tie-2, regardless of the individual patient' s profile, was observed in all cases of GCTTS. Six sets of double immunohis tochemical stainings for Tie-1/Tie-2 and fibronectin, CD68, or CD34 were ca rried out to determine the phenotype of Tie-1 and Tie-2-positive tumor comp onents. In these studies, both Tie-1 and Tie-2 immunoreactivity were widely observed in the fibronectin-positive fibroblastic and the CD68-positive hi stiocytic mononuclear cells, as well as in the osteoclast-like giant cells. In tumor vasculature, Tie receptors were expressed in the CD34-positive en dothelial cells possessing proliferating cell nuclear antigen (PCNA) immuno reactivity. We also evaluated the correlation of Tie-1/Tie-2 expression and proliferating cells in GCTTS by using double staining of Tie-1/Tie-2 toget her with PCNA. Overexpression of PCNA immunoreactivity was frequently found in Tie receptors-positive cells with no obvious differences in the express ion pattern of Tie-1 and Tie-2. These findings suggest the possible involve ment of Tie receptors in the pathogenesis of GCTTS other than solely via th eir involvement in angiogenesis and subsequent vascularization. It was demo nstrated that Tie-2 immunoreactivity was restricted to the fibroblastic, bu t not histiocytic, phenotype in RA synovium, suggesting different regulator y control of Tie-2 expression in GCTTS and RA synovium. Overexpression of T ie receptors in GCTTS may imply a biological role for these receptors in sy novial proliferation.