【摘要】 目的:研究骨肉瘤中环氧合酶-2(cyclooxygenase 2,Cox-2)与缺氧诱导因子1α(hypoxia-inducible factor 1 alpha,HIF-1α)的蛋白表达及其与临床病理特征、生存预后的关系;探讨其在肿瘤形成、发展过程中的可能机制。方法:筛选不含硬骨组织,未经脱钙处理的骨肉瘤标本59例,进行临床、病理特征分期,并行术后跟踪。应用免疫组织化学方法检测肿瘤组织中Cox-2与HIF-1α的表达,绘制Kaplan-Meier生存曲线,结果:Cox-2和HIF-1α在骨肉瘤中的表达率分别为69.49%和38.98%,在对照组中的表达均为阴性,差异有统计学意义(P<0.01和P<0.05)。Cox-2的表达与骨肉瘤临床分期呈正相关(P<0.05),HIF-1α的表达与年龄相关(P<0.01)。Cox-2的表达与HIF-1α的表达呈正相关。在Cox-2阳性组和阴性组中,HIF-1α的阳性表达率分别为56.10%和0,差异有统计学意义(P<0.01)。组间生存率差异显示术后生存期长短与Cox-2和HIF-1α的表达呈负相关,Cox-2和HIF-1α表达阳性者的术后累积生存率均低于阴性者,差异有统计学意义(P<0.05和P<0.01)。结论:Cox-2和HIF-1α在骨肉瘤组织中均为高表达,两者的表达与肿瘤的发生、发展有关,可能共同促进了肿瘤的恶性进展。Cox-2和HIF-1α阳性表达者的术后生存率较低,其表达可以反映骨肉瘤的预后。更多还原

【Abstract】 Objective: This study aims to investigate the protein expressions of cyclooxygenase-2(Cox-2) and hypoxia-inducible factor 1 alpha(HIF-1α) and their correlations with the clinicopathological features of osteosarcoma and tries to reveal the potential mechanisms for the formation and progression of osteosarcoma.Methods: We screened 59 typical samples of osteosarcoma tissues without os and decalcification treatment.They were grouped according to the clinicopathologic characteristics and were followed up post surgery.Expression of Cox-2 and HIF-1alpha were detected by immunohistochemistry.The results were evaluated by χ2 analysis and Spearman rank correlation analysis.The postoperative survival rates were calculated by Kaplan-Meier survival curve and the differences between groups were analyzed by Log-Rank method.Results: The positive expression rates of COX-2 and HIF-1α in osteosarcoma were 69.49% and 38.98%,respectively,which were significantly different compared with negative expression in control group(P<0.01 and 0.05).The expression of Cox-2 in osteosarcoma positively correlated with the clinical stage(P<0.05) and the expression of HIF-1α correlated with the age of patients(P<0.01).The expressions of Cox-2 and HIF-1α were closely associated with the histological classifications.In COX-2-and HIF-1α-positive groups,the total positive rates(16.67% and 0%) of intraosseous well-differentiated and parosteaosteosarcoma were significantly lower than that of any others(73.33%,and 43.18%),respectively.The difference was significant(and P<0.01 and P<0.05).The expression of Cox-2 had positive correlation with HIF-1alpha.The positive co-expression of both HIF-lα and Cox-2 was 38.98%.There was 30.50% osteosarcoma tissues had no expression of both Cox-2 and HIF-1alpha.The positive expression rates of HIF-lα in Cox-2-positive and Cox-2-negative groups were 56.10% and 0%,respectively.The difference was significant(P<0.01).The postoperative survival period was negatively associated with the expression of Cox-2 and HIF-1α.The postoperative accumulative survival rates were significantly lower in Cox-2-and HIF-1alpha-positive patients compared with those in Cox-2-and HIF-1alpha-negative patients(P<0.05 and P<0.01,respectively).Conclusion: Cox-2 and HIF-1α were over-expressed in osteosarcoma.Their expressions are related with the formation and progression of tumor and may have synergistic effects in prompting the malignant development of osteosarcoma.The patients with positive expression of Cox-2 and HIF-1α have lower postoperative accumulative survival rates.Their expressions may be useful prognostic factors for osteosarcoma.更多还原