CAJ | 학술논문

目的研究新发胶质母细胞瘤中肿瘤不同部位MGMT基因启动子甲基化及其蛋白表达关系及区域差异性.方法在30例新发胶质母细胞瘤肿瘤不同部位采取2～4块标本,其中5例在术中神经导航引导下采取.甲基化特异性PCR(MSP)法检测标本中MGMT基因启动子甲基化状况,免疫组化法(IHC)检测组织切片MGMT蛋白表达情况.结果 43.56%(44/101)检测肿瘤组织中出现MGMT基因启动子甲基化,免疫组化检测(阴性,细胞弱着色＜10%或细胞无着色;弱阳性,10%≤细胞着色≤50%;强阳性,细胞着色＞50%)发现MGMT蛋白表达情况分别为阴性(32.67%),弱阳性(43.56%),强阳性(23.76%).MGMT基因启动子甲基化与其蛋白表达无明显相关性(x2=2.905,P=0.088).在肿瘤不同取材部位组织之间57%的患者(17/30)MGMT蛋白表达水平与37%患者(11/30)启动子甲基化存在不均一性.结论 MGMT基因启动子甲基化可能不是MGMT蛋白表达的惟一调节因素.同一肿瘤不同取材部位组织MGMT蛋白表达与其基因启动子甲基化水平不均一性的结果质疑了单一取材标本的检测结果及其对临床治疗方案选择的指导意义.
목적 연구신발효질모세포류중종류불동부위MGMT기인계동자갑기화급기단백표체관계급구역차이성.방법 재30례신발효질모세포류종류불동부위채취2～4괴표본,기중5례재술중신경도항인도하채취.갑기화특이성PCR(MSP)법검측표본중MGMT기인계동자갑기화상황,면역조화법(IHC)검측조직절편MGMT단백표체정황.결과 43.56%(44/101)검측종류조직중출현MGMT기인계동자갑기화,면역조화검측(음성,세포약착색＜10%혹세포무착색;약양성,10%≤세포착색≤50%;강양성,세포착색＞50%)발현MGMT단백표체정황분별위음성(32.67%),약양성(43.56%),강양성(23.76%).MGMT기인계동자갑기화여기단백표체무명현상관성(x2=2.905,P=0.088).재종류불동취재부위조직지간57%적환자(17/30)MGMT단백표체수평여37%환자(11/30)계동자갑기화존재불균일성.결론 MGMT기인계동자갑기화가능불시MGMT단백표체적유일조절인소.동일종류불동취재부위조직MGMT단백표체여기기인계동자갑기화수평불균일성적결과 질의료단일취재표본적검측결과 급기대림상치료방안선택적지도의의.
Objective To study the correlation of MGMT gene promoter methylation and protein expression and their regional variation in different specimens obtained from different regions within the tumor in patients with newly diagnosed glioblastoma. Methods Two to four samples in the same tumor were collected from different regions in 30 patients with newly diagnosed glioblastoma patients. In five patients among them,mutispecimens were obtained under assistance of neuronavigation system during the operation. In all samples,MGMT promoter profile were analyzed by Methylation - specific polymerase - Chain - reaction analysis, MSP ,while MGMT protein expression was detected in tissue sections by immunohistochemistry,IHC. Results MGMT promoter methylation was detected in 43. 56% (44/101) specimens. MGMT protein expression in tissue sections was assessed and scored:(1 :no or positive tumor cells < 10%, 2: ≥ 10% ≤50% ,3: > 50%) ,The rate of MGMT staining with a score 1,2,3 in all of tumor sections was 32. 67% ,43.56% ,23. 76% respectively. No significant correlation between MGMT protein expression and promoter methylation(x2 =2. 905, P =0.088) was found. The regional heterogeneity of MGMT protein expression within the same tumor was in 57% (17/30) patients ;and the regional heterogeneity of gene promoter methylation was in37%(11/30)patients. Conclusions MGMT promoter methylation is probably not the only modulating element in MGMT protein expression. The heterogeneity of MGMT protein expression and its promoter methylation in the same tumor questions their guiding significance in making therapeutic scheme for individual patients with malignant glioma in clinical practice.