MGMT和Ki-67在胶质母细胞瘤中的表达对ACNU化疗预后的影响

背景与目的:胶质母细胞瘤是预后极差的常见颅内恶性肿瘤,手术切除、放疗和化疗联合应用是常规治疗方法;Ki-67是肿瘤细胞生长活跃程度的标志,与胶质瘤的分级显著相关;O6-甲基鸟嘌呤DNA甲基转移酶(MGMT)是一种DNA修复蛋白,其表达影响肿瘤对化疗药的敏感性。本研究通过免疫组织化学方法对胶质母细胞瘤的Ki-67和MGMT进行检测,探讨其对胶质母细胞瘤化疗预后的影响。方法:总结39例脑胶质母细胞瘤患者的性别、年龄、术前Karnofsky评分、生存时间等;将患者手术切除标本石蜡切片进行Ki-67和MGMT的免疫组织化学染色,计算细胞核染色阳性率;多元逐步回归分析法判断Ki-67和MGMT的表达与患者生存时间的关系。结果:本组病例男22例,女17例;年龄21～75岁,平均54.0岁;生存时间6～38个月,平均19.3个月,中位生存期17.0个月。Ki-67在所有标本有不同程度的表达,表现为胞核明显染色,Ki-67阳性率4.0%～26.6%,平均10.5%。MGMT除2例外均有不同程度表达,胞浆染色较淡,胞核可见浓染,MGMT胞核阳性率0%～51.4%,平均21.2%。Ki-67阳性率与生存时间无相关性。MGMT胞核阳性率与生存时间呈负相关(P=0.002)。结论:Ki-67在胶质母细胞瘤表达与肿瘤的预后无关。MGMT在胶质母细胞瘤表达与肿瘤化疗后的预后有关,MGMT的检测对胶质母细胞瘤术后化疗可能有指导意义。

Correlation of O^6-Methylguanine-DNA Methyltransferase and Ki-67 with Prognosis of Glioblastoma Patients Treated with ACNU

BACKGROUND & OBJECTVES: As the most common malignant primary brain tumor with poor prognosis, glioblastoma is generally treated with surgical removal, radiotherapy and chemotherapy. Ki-67 antigen, an indicator of tumor cell proliferation, is correlated with glioma grading; and O6-Methylguanine-DNA Methyltransferase(MGMT), a DNA repair protein, contributes tumor resistance to chemotherapy. This study is to evaluate the correlation of the prognosis of glioblastoma after ACNU chemotherapy with Ki-67 and MGMT by immunohistochemical determination. METHODS: The sex, age, pre-operation Karnofsky performance status and survival time of 39 glioblastoma patients were recorded, then Ki-67 and MGMT were determined immunohistochemically for paraffin sections. Correlation of Ki-67 and MGMT with patient survival time was analyzed by multiple stepwise regression procedure. RESULTS: There were 22 male and 17 female glioblastoma patients with 54.0 years of verage age and 19.3 months of average survival. Ki-67 antigen was expressed in all samples as nuclear immunostaining with MIB-1 labeling index of 4.0%-26.6%. MGMT was expressed to a various extent in all but two samples, where MGMT mainly accumulated in the nuclei, and the percentage of labeled tumor cells was 0%-51.4% with average of 21.2%. No correlation was found between Ki-67 labeling index and survival time. Negative correlation was demonstrated statistically between MGMT labeling index and survival time (P=0.002). CONCLUSIONS: There is no correlation between Ki-67 antigen expression in glioblastoma and patient survival. MGMT expression in glioblastoma is correlated with tumor prognosis after ACNU treatment, and immunohistochemical assessment of MGMT may guide chemotherapy in clinical practice.