目的探讨缺氧诱导因子1α(HIF-1α)蛋白、多药耐药相关蛋白1(MRP1)在脊索瘤中的表达水平及其与脊索瘤病理特征和放化疗抵抗之间的关系。方法收集2000年1月-2008年12月接受手术治疗的50例脊索瘤患者的肿瘤组织石蜡标本,另取15例骨软骨瘤标本作为对照。50例脊索瘤患者中男35例,女15例;年龄17~77岁,平均53.3岁;原发病例26例,复发病例24例;病理类型包括普通型48例,去分化型1例,外周型1例。采用免疫组化Envision法检测HIF-1α、MRP1蛋白表达情况,分析其与放化疗抵抗的关系,并探讨HIF-1α、MRP1表达与脊索瘤临床病理特征的关系。结果50例脊索瘤组织HIF-1α、MRP1的阳性表达率分别为80%和74%,均明显高于骨软骨瘤组织(分别为20%和27%,P〈0.01)。相关性分析显示,脊索瘤组织中HIF-1α与MRP1的表达呈正相关关系(r=0.80,P〈0.01)。脊索瘤组织中HIF-1α、MRP1的表达水平与患者性别、年龄、发病次数及肿瘤大小、部位、分化程度、分期、淋巴结转移均无明显关系。结论脊索瘤组织中HIF-1α和MRP1表达明显增高,且两者表达水平呈正相关,其过度表达可能在脊索瘤的放化疗抵抗中具有重要作用。
Objective To investigate the expression of hypoxia inducible factor-1α(HIF-1α)and multidrug resistance protein 1(MRP1)in chordoma,and explore the relationship between the expressions with its clinicopathological features and resistance to chemotherapy and radiotherapy.Methods The paraffin-embedded tissue samples were collected from 50 patients with chordoma,who underwent surgical operation from Jan.2000 to Dec.2008(35 males and 15 females,age ranged from 17 to 77 with mean of 53.3 years).15 samples of osteochondroma were used as control.Of the 50 patients,26 were primary cases and 24 recurrent cases;the pathological types included common type(48 cases),poorly-differentiated(1 case)and peripheral-type(1 case).The expression of HIF-1α and MRP1 was detected with immunohistochemical technique(ChemMateTM Envision),the relationship was statistically analyzed between the expression with clinicopathological features and resistance to chemotherapy and radiotherapy of chordoma.Results The expression rates of HIF-1α and MRP1 in 50 patients were 80% and 74%,respectively,and they were significantly higher than those in the control subjects(patients with osteochondroma,20% and 26.7%,respectively,P〈0.01).There existed positive correlation between the expression of HIF-1α and the expression of MRP1(r=0.8,P〈0.01),but no obvious correlation was found between the expression of HIF-1α,MRP1 and patients' age,recurrent rate,tumor size and site,differentiation degree and stage,and lymphatic metastasis.Conclusions The expressions of HIF-1α and MRP1 are obviously increased in chordoma,and a positive correlation is found between the tumor and the expressions.The overexpression of HIF-1α and MRP1 may play an important role in resistance of the tumor to chemotherapy and radiotherapy,and they might serve as a potential target in an attempt to evert the resistance of the temor to chemotherapy and radiotherapy in patients.