Influence Of Neoadjuant Chemotheratpy On Biological Behaviour Of Osteosarcoma And Clinical Meaning

Objective:To study the influence of neoadjuvant chemotherapy on the expression of Cyclin D1, Bcl-2, PCNA and P-gp in osteosarcoma cells and the radiological changes of osteosarcoma. To investigate the relationship between the biological behaviour changes and TCNR,prognosis.Methods:Using immunohistochemical staining the expression of Cyclin D1, Bcl-2, PCNA and P-gp were examined in the 23 cases of osteosarcoma. TCNR were calculated and 21cases were done follow-up with a mean time of 43 months. The relationships between their expression and TCNR, prognosis were analyzed. Dynamical radiological examinations were done in 23 patients during preoperative chemotherapy. The radiological scoring system was established and radiological scores before and after chemotherapy were calculated. The relationships between the radiological scores and TCNR, prognosis were analyzed. The relationships between the radiological changes and the expression of Cyclin D1, Bcl-2, PCNA and P-gp after chemotherapy were analyzed.Results:1. The positive expression rate of Cyclin D1,Bcl-2,PCNA and P-gp before chemotherapy was 56.5%,73.9%,87.0%,13.0%respectively. That positive expression rate after chemotherapy was 47.8%,39.1%,47.5%,47.8%respectively. The positive expression rate of Bcl-2,PCNA after chemotherapy was much lower than that of pre-chemotherapy(P <0.05). After chemotherapy the expression rate of P-gp was higher(P< 0.05)and the expression of Cyclin D1 was no difference(P> 0.05).2. No relation was found between the expression of Cyclin Dl,Bcl-2,P-gp and TCNR before or after chemotherapy (P> 0.05). There were no relation between the expression of PCNA and the TCNR before chemotherapy(P> 0.05). There were negative correlation between the express of PCNA and TCNR after chemotherapy(P< 0.05). 3. No relationship existed between the expression of Bcl-2,PCNA,P-gp and prognosis before chemotherapy, but the relation was found after chemotherapy. The higher of the positive expression rate of Bcl-2,PCNA and P-gp the better of the prognosis. There were no relation between the expression of Cyclin D1 and prognosis before or after chemotherapy.4. The post-chemotherapy radiological scores were much higher than that of pre-chemotherapy(P< 0.05). The relation was found between the post-chemotherapy radiological scores and TCNR and prognosis after chemotherapy:the higher of the post-chemotherapy radiological scores the better of the prognosis.5. There were negative correlation between the radiological scores and the expression of Bcl-2,PCNA,P-gp after chemotherapy. No relationship existed between the expression of Cyclin D1.Conclusions:1. Chemotherapy could inhibit proliferation and induce apoptosis on osteosarcoma cells. At the same time, due to the overexpression of the MDR, the drug resistance of the osteosarcoma cells was increased.2. The determination of Cyclin D1,Bcl-2,PCNA and P-gp before chemotherapy could not evaluate the curative effect of the chemotherapy, but using the determination of Bcl-2,PCNA and P-gp after chemotherapy could evaluate the curative effect of the chemotherapy.3. On the cell molecular level it was confirmed that the radiological signs of osteosarcoma after chemotherapy were on the base of tumor cells'biological behavior. We could evaluate the therapeutic effect by analyzing the radiological signs.Significance:There was no report on the influence of neoadjuvant chemotherapy on the expression of gene in osteosarcoma cells currently. Our study confirmed that there was significant relationship between the curative effect of the chemotherapy and the expression of gene and we could predict the therapeutic effect by analyzing the expression of gene after chemotherapy in order to adjust therapeutic regimen in time.