cIAP2 expression and clinical significance in pigmented villonodular synovitis

Pigmented villonodular synovitis (PVNS) is a rare hyperplasia disease of the synovium with a predilection for the knee in either a localized (LPVNS) or a diffuse form (DPVNS). But the exact cause is not clear. The aim of this study was to explore the relationship between the expression of cellular inhibitor of apoptosis 2 (cIAP2) and proliferation, apoptosis, invasive growth and postoperative recurrence in PVNS. Clinical significance of cIAP2 expression in synovium from 63 patients' knee joints with PVNS (40 DPVNS; 23 LPVNS) were investigated with 20 normal subjects acting as controls. The cIAP2 gene was screened by Human Cancer Pathway Finder PCR Array and real-time polymerase chain reaction (RT-PCR). We also used immunohistochemistry to detect cIAP2 and proliferating cell nuclear antigen (PCNA) protein expression and analyzed their relationship with PVNS type, invasive growth, and postoperative recurrence. The expression of cIAP2, PCNA, caspase-8, caspase-9 and caspase-3 protein was tested in Western blot. Screening results of Human Cancer Pathway Finder PCR array and RT-PCR showed significantly more cIAP2 mRNA in DPVNS synovium than in normal or LPVNS synovium (P < 0.05). Immunohistochemistry and western blot showed that the cIAP2 protein expression level in DPVNS was significantly higher than in LPVNS tissue (P < 0.01). As cIAP2 expression increased, the expression of PCNA increased (P < 0.05) and expression of cleaved caspase-3, -8, -9 decreased (P < 0.01). cIAP2 and PCNA overexpression were found to be related to ligament and bone erosion in PVNS and to disease recurrence (P < 0.05). This study suggested that cIAP2 overexpression plays an important role in the anti-apoptotic, proliferative and invasive growth of PVNS, which may account for the recurrence and poor prognosis of DPVNS.