PCR Array Screening Of Pigmented Villonodular Synovitis And Clinical Significance Of CIAP2 Expression

Objective: To investigate the differential expressions of PVNS genes by Human Caner Pathway Finder PCR Array and to explore the relationship between the expression of CIAP2 and proliferation,apoptosis,invasive growth and postoperative recurrence in PVNS.Methods: 63 patients with PVNS were diagnosed and analyzed.Among them,40 cases were diffuse PVNS(DPVNS),23 cases were localized PVNS(LPVNS)and 20 cases were normal subjects.The gene was screened by QIAGEN(German)Human CancerPathway Finder PCR Array.Then,the results were verified by real-time polymerase chain reaction PCR(RT-PCR).The expression of CIAP2(BIRC3)gene,which was highly expressed by apoptotic pathway,was further investigated.We also used immunohistochemistry to detect CIAP2 and 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.Results: 63 patients with PVNS were triple diagnosed by clinical,imaging and pathology.PCR Array analysis showed that DPVNS synovial tissue and normal synovial tissue gene expression was significantly different,mainly related to tumor signaling pathway in angiogenesis,anti-apoptosis,promote proliferation,DNA damage repair related genes,of which 17 genes going up and 11 genes going down(P <0.05).The relative expression of CIAP2 mRNA in DPVNS synovial tissue was significantly higher than that in normal tissues(P <0.05).RT-PCR showed consistent results,CIAP2 mRNA expression in DPVNS significantly higher than that in normal tissue and LPVNS(P <0.01).In Immunohistochemistry,the expression of CIAP2 and PCNA protein was low in LPVNS,usually negative in normal tissue and high in DPVNS.In addition,they were significantly higher in DPVNS than in LPVNS(P<0.01).In PVNS,invasion of ligament and bone and postoperative recurrence rate were significantly increased with high CIAP2 and PCNA expression(P <0.05).PCNA protein's increase was in accordance with CIAP2 protein's increase(P <0.01).Western blot analysis showed that the expression of CIAP2 and PCNA protein in DPVNS synovial tissue was significantly higher than that in LPVNS synovial tissue,which was consistent with immunohistochemical results.The expression of Cleaved caspase-3,-8 and-9 was significantly lower than that of LPVNS(P <0.01).The expression of CIAP2 and PCNA protein in LPVNS synovial tissue was higher than that in normal synovial tissue(P <0.05),but the expression of Cleaved caspase-3,-8 and-9 was higher than that of normal synovial tissue(P <0.01).Conclusions: The gene expression of DPVNS synovial tissue was significantly different from that of normal synovial tissue,which mainly involves the genes related to angiogenesis,anti-apoptosis,pro-proliferation and DNA damage repair in tumor signaling pathway.The expression of CIAP2 mRNA in DPVNS was significantly higher than that in LPVNS and normal synovial tissue.The expression of CIAP2 mRNA in LPVNS was significantly higher than that in normal synovial tissue.The expression of CIAP2 and PCNA protein in the synovial tissue of DPVNS was significantly higher than that of LPVNS,and the expression of cleaved caspase was significantly lower than that of LPVNS.With the expression of CIAP2 upregulated,invasion of ligament and bone showed more often and postoperative recurrence rate rised.These results might suggest that CIAP2 plays an important role in anti-apoptotic,proliferative and invasive growth of PVNS,which may be one of the important causes of recurrence and poor prognosis of DPVNS.