| Objective: Thymic epithelial tumors are potential invasive and at anterior mediastinum frequently,and their histological and biological characteristics are complicated.Surgical resection is a good treatment method now.There are still some patients recurrence after surgery.Our subject is about to detect the methylation and protein expression of O~6-methylguanine DNA methyl transferase from TETs to find some factors as the prognosis of TETs by methylation specific polymerase chain reaction(MSP)and immunohistochemistry(IHC).And we evaluate the correlation between two test results and the prognosis of TETs to provide more information for the diagnosis and therapy of clinical work.Methods:1 Methylation status of MGMT gene promoter in 94 thymic epithelial tumors cases was detected by methylation specific polymerase chain reaction(MSP).2 The expression of MGMT in thymic epithelial tumor tissue was detected by immunohistochemistry(IHC).3 Getting information from patients by medical clinical records and followed-up data were reviewed.4 SPSS21.0 was applied to analyzing the results of the experiments results.Results:1 MGMT methylation and loss of expressionWe found that 25/35(71.4%)tumors with reduced MGMT expression,showed MGMT methylation.On the other hand,there were 17/59(28.8%)tumors with normal MGMT expression,showed MGMT methylation.There is significant correlation between MGMT methylation and loss of its expression(P<0.05).2 WHO calssification and MGMT methylation and loss of expressionMGMT methylation was significantly more frequent in thymic carcinoma than in thymoma(20/28,71.4% versus 22/66,33.3%;P < 0.05).The loss of expression of MGMT protein was significantly more frequent in thymic carcinoma than in thymoma(22/28,78.6% versus 13/66,19.7%;P < 0.05).No correlation between MGMT methylation and histological subgroups of thymoma;1 of 6(16.7%)in type A,6/16(37.5%)in type AB,4/18(22.2%)in type B1,7/16(43.8%)in type B2 and 4/10(40.0%)in type B3.No correlation between loss of MGMT expression and histological subgroups of thymoma;0 of 6(0%)type A,3 of 16(18.8%)type AB,3 of 18(16.7%)type B1,3 of 16(18.8%)type B2,3 of 10(30.0%)type B3.3 Masaoka’s staging and MGMT methylation and loss of expressionMGMT methylation of TET was 4/30(13.3%)in Stage I,7/19(36.8%)in Stage II,10/20(50%)in Stage III and 21/25(84%)in Stage IV.MGMT hypermethylation was significantly more frequent in advanced tumor(Stages III and IV)than in early tumor(Stages I and II)(31/45,68.9% versus 11/49,22.4%;P < 0.05).Regarding thymoma,MGMT methylation was detected in 3/28(10.7%)in Stage I,5/11(45.5%)in Stage II,5/14(35.7%)in Stage III and 9/13(69.2%)in Stage IV.MGMT hypermethylation was significantly more frequent in advanced tumor(Stages III and IV)than in early tumor(Stages I and II)(14/27,51.9% versus 8/39,20.5%;P < 0.05)Abnormal MGMT expression in TET was detected in 4/30(13.3%)in Stage I,8/19(42.1%)in Stage II,8/20(40.0%)in Stage III and 15/25(60.0%)in Stage IV.The loss of expression of MGMT protein in TET was significantly more frequent in the advanced tumor(Stages III and IV)than in the early tumor(Stages I and II)(23/45,51.1% versus 12/49,24.4%).Regarding thymoma,abnormal MGMT expression was detected in 2/28(7.1%)in Stage I,3/11(27.3%)in Stage II,5/14(35.7%)in Stage III and 3/13(23.0%)in Stage IV.There was no significant difference in loss of MGMT expression between advanced and early thymoma(8/27,29.6% versus 5/39,12.8%;P>0.05).4 The relationship between myasthenia gravis and MGMT methylationThe rate of methylation of MGMT was detected from thymic epithelial tumors in patients with MG is 60%(12/20)and the rate from the thymic epithelial tumors in patients with no MG is 40.5%(30/74).No correlation between MG and the status of MGMT in thymic epithelial tumors.The rate of abnormal MGMT expression was detected from thymic epithelial tumors in patients with MG is 55.0%(11/20)and the rate from the thymic epithelial tumors in patients with no MG is 32.4%(24/74).No correlation between MG and abnormal MGMT expression in thymic epithelial tumors.There is no correlation between thymic epithelial tumors in patients with MG and WHO histologic classification(P>0.05).Type A 0.0%(0/20),type AB 0.0%(0/20),type B1 15.0%(3/20),type B2 25.0%(5/20),type B3 15.0%(3/20),thymic carcinoma 45.0%(9/20).There is no correlation between thymic epithelial tumors in patients with MG and Masaoka clinical stage(P>0.05).There are 7 cases(35.0%)with MG in early tumors(Stages I and II)and 13 cases(65.0%)with MG in advanced tumors(Stages III and IV).5 Overall survivalThere was no significant difference in overall survival between mthylated and unmethylated cases(69% versus 89%;5 years survival).There was no significant difference in overall survival between cases with loss of MGMT expression and cases with normal expression(76% versus 84%;5 years survival).The survival rate was significantly higher in thymoma than in thymic carcinoma(84.6%versus 54.7%;P<0.05),and which was sinnificantly higher in early tumor than in advanced tumor(85.0% versus 64.3%;P<0.05).6 Multivariate analysis of correlation between methylation and stage and histologyOur model included parameters age,gender,histology,clinical stage and MG.Only thymic carcinoma(P<0.001)and advanced stage(P<0.05)was independently associated with MGMT hypermethylation.Conclusions: MGMT methylation is more frequent in thymic carcinoma than in thymoma.Furthermore,there is a significant correlation between MGMT methylation and aggressiveness of TET. |
PDF Full Text Request