抑癌基因磷酸酶与张力蛋白同源物、巨噬细胞移动抑制因子在高分化子宫内膜样腺癌及癌前病变中表达意义的探讨

Significance of expressions of PTEN and MIF in highly differentiated endometrioid adenocarcinoma and cervical precancerous lesion

目的探讨抑癌基因磷酸酶与张力蛋白同源物（PTEN）、巨噬细胞移动抑制因子（MIF）在高分化子宫内膜样腺癌及癌前病变中表达的意义。方法 126例高分化子宫内膜样腺癌及癌前病变、10例正常的增生期子宫内膜,应用RT-PCR方法测定中PTEN mRNA,应用免疫组织化学检测PTEN、MIF蛋白的表达情况。结果高分化宫内膜样腺癌组、子宫内膜不典型增生组PTEN mRNA表达率明显低于增生期子宫内膜组,差异有统计学意义（t值分别为23.39、24.06,均P〈0.01）;高分化宫内膜样腺癌PTEN mRNA表达率低于子宫内膜不典型增生组,但差异无统计学意义（t=1.70,P〉0.05）。在增生期子宫内膜组、子宫内膜轻/中度不典型增生组、子宫内膜重度不典型增生组及高分化宫内膜样腺癌组,PTEN蛋白表达率逐渐降低,MIF蛋白表达率依次升高,两者表达呈显著负相关（rs=-0.172 7,P〈0.05）。PTEN蛋白在病变组表达率与增生期子宫内膜组比较差异均有统计学意义（χ^2值分别为7.07、12.07、17.07,P〈0.01）,但在病变组之间比较差异无统计学意义（χ^2值分别为0.73、1.85和0.21,均P〉0.05）;MIF蛋白在子宫内膜重度不典型增生组和高分化宫内膜样腺癌组阳性率显著高于子宫内膜轻/中度不典型增生组和增生期子宫内膜组,差异有统计学意义（χ^2值分别为4.01、6.35、5.91、7.90,P〈0.05）,但在子宫内膜重度不典型增生组和高分化宫内膜样腺癌组比较差异无统计学意义（χ^2值分别为1.29、0.08,均P〉0.05）。结论 PTEN与MIF蛋白异常表达共同参与子宫内膜癌的发生、发展,是子宫内膜样腺癌发生的早期事件。联合检测PTEN与MIF蛋白表达情况对子宫内膜样腺癌的发生、发展具有一定的预测作用,但对子宫内膜重度不典型增生和宫内膜样腺癌鉴别诊断帮助不大。

Objective To explore the significance of expressions of phosphatase and tensin homolog（ PTEN） and macrophage migration inhibition factor（ MIF） in highly differentiated endometrioid adenocarcinoma and cervical precancerous lesion. Methods A total of 126 cases with highly differentiated endometrioid adenocarcinoma and cervical precancerous lesion,10 cases with normal endometrium during proliferative stage were selected,RT-PCR was used to detect PTEN mRNA,immunohistochemical staining was used to detect expressions of PTEN protein and MIF protein. Results The expression rates of PTEN mRNA in highly differentiated endometrioid adenocarcinoma group and endometrial atypical hyperplasia group were statistically significantly lower than that in proliferative stage group（ t = 23. 39,P〈0. 01; t =24. 06,P〈0. 01）. The expression rate of PTEN mRNA in highly differentiated endometrioid adenocarcinoma group was lower than that in endometrial atypical hyperplasia group,but there was no statistically significant difference（ t = 1. 70,P〉 0. 05）. In proliferative stage group,mild to moderate endometrial atypical hyperplasia group,severe endometrial atypical hyperplasia group,and highly differentiated endometrioid adenocarcinoma group,the expression rates of PTEN protein decreased gradually,while the expression rates of MIF protein increased gradually,the expression rate of PTEN protein was negatively correlated with the expression rate of MIF protein（ rs=-0. 172 7,P〈0. 05）. There was statistically significant difference in the expression rate of PTEN protein between cervical lesions groups and proliferative stage group（ χ^2= 7. 07,12. 07,17. 07,P〈0. 01）,but there was no statistically significant difference among cervical lesions groups（ χ^2=0. 73,1. 85,0. 21,P〉0. 05）. The positive rates of MIF protein in severe endometrial atypical hyperplasia group and highly differentiated endometrioid adenocarcinoma group were statistically significantly higher than those in mild to moderate endometrial atypical hyperplasia group and proliferative stage group（ χ^2= 4. 01,6. 35,5. 91,7. 90,P〈0. 05）. There was no statistically significant difference in the positive rate of MIF protein between severe endometrial atypical hyperplasia group and highly differentiated endometrioid adenocarcinoma group（ χ^2= 1. 29,0. 08,P〉0. 05）. Conclusion Both PTEN protein and MIF protein are involved in oncogenesis and development of endometrial adenocarcinoma,which are early events of endometrioid adenocarcinoma,joint detection of PTEN protein and MIF protein can predict the oncogenesis and development of endometrioid adenocarcinoma to a certain extent,but it has no significant impact on differential diagnosis between atypical hyperplasia of endometrium and highly differentiated endometrioid adenocarcinoma.