Influence Of Chemotherapy On Expression Of α_v Integrin, VEGF And PCNA In Osteosarcoma

Objective:The aim of this study was to investigate the influence of chemotherapy with adriamycin(ADM), Cis-diam inodichloropkatin(DDP) and Ifosfamide (IFO) on expression of αv integrin, VEGF and PCNA in osteosarcoma and to evaluate their roles in invasion, metastasis and relapse of osteosarcoma after chemotherapy.Methods: Expression of αv integrin, VEGF and PCNA were assessed immunohistochemically in the experimental groups including paraffin sections of 20 patients with non-treated osteosarcoma and 31 cases after chemotherapy with ADM, DDP and IFO(ADI). Paraffin sections of 10 patients with exostosis and 10 cases with normal bone tissues as the control groups were drawn at random. The correlation between expression of αv integrin, VEGF and PCNA in osteosarcoma cells and recurrence,soft tissue invasion and metastasis of the tumor was evaluated. Potential prognostic factors for osteosarcoma after chemotherapy were analysed by using the Logistic stepwise regression model.Results:1. Expression of αv integrin, VEGF and PCNA in osteosarcoma cells were markedly higher than those in exostosis and normal bone tissues(P<0. 05).2. There was positive correlation between α v integrin expression in chemotherapy-treated osteosarcoma cells and the Enneking stage, relapse and soft tissue invasion of tumor(P<0.05)3. Expression of VEGF in osteosarcoma after chemotherapy was associated with the Enneking stage, recurrence, invasion and primarymetastasis of osteosarcoma (p<0.05),4. There was positive correlation between expression of α v integrin and VEGF in osteosarcoma (P<0.05), which both dropped after chemotherapy (P<0. 05).5. There was no statistically significant difference between expression of PCNA before chemotherapy and after chemotherapy(P>0.05). Expression of α v integrin was significantly positive correlaton with that of PCNA(P<0. 05) in chemotherapy-treated osteosarcoma.6.The results of Logistic stepwise regression model suggested that integrin α v might be one of a set of independent variables which influenced relapse and invasion of osteosarcoma, meanwhile, the Enneking stage be another one which was correlative with invasion of osteosarcoma.Conclusions: These results suggest that expression of αv integrin, VEGF and PCNA may act as assistant indicators in diagnosis of osteosarcoma. Expression of α v integrin and VEGF in osteosarcoma cells which drop significantly after chemotherapy reveals that chemotherapy appears to regulate biological behavior of osteosarcoma cells through down-regulate expression of α v integrin and VEGF. There is somewhat positive correction between expression of α v integrin and VEGF in chemotherapy-treated ostosarcoma, which indicates they are likely to cooperatively regulate biological behavior of tumor for response to chemotherapy including malignant phenotype, invasion and relapse. Expression of α v integrin after chemotherapy might be an independent factor for relapse and invasion of osteosarcoma, meanwhile, malignance of tumor be another possible one for invasion of osteosarcoma. There is no difference between expression of PCNA before chemotherapy and after chemotherapy. Expression of α v integrin is related to that of PCNA which has been proved to be an essential component of proliferation and repair of tumor cells damage. Therefore, further study of these variables mentioned above may bevaluable to understand the roles of α v integrin, VEGF and PCNA in chemotherapy-treated osteocarcoma, and may yield prognostic information as well as new therapeutic strategies for the treatment of osteosarcoma.