Nakamizo Akira, Inamura Takanori, Ikezaki Kiyonobu, Yoshimoto Koji, Inoha Satoshi, Mizoguchi Masahiro, Amano Toshiyuki, Fukui Masashi
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
J Neurooncol. 2002 Apr;57(2):105-14. doi: 10.1023/a:1015705305540.
Both cell proliferation and cell death occur simultaneously in tumor tissue, and extent of tumor growth reflects the net balance of these events. We correlated cell proliferation, spontaneous cell death, and alterations in tumor suppressor proteins with one another and with survival of patients with primary astrocytic tumors. In 39 astrocytic tumor specimens (6 pilocytic astrocytomas, 14 fibrillary astrocytomas, 9 anaplastic astrocytomas, and 10 glioblastomas), we determined the MIB-1 labeling index, the apoptotic ratio according to nick end labeling with morphologic confirmation, the p53 labeling index, and the presence of p53 or PTEN mutations. MIB- I labeling indices of pilocytic astrocytomas, fibrillary astrocytomas, anaplastic astrocytomas, and glioblastomas were 0.30+/-0.32; 1.84+/-1.87; 19.3+/-6.42; and 28.0+/-14.5 (mean +/- SD), respectively. Corresponding apoptotic ratios were 17.9+/-5.16; 3.96+/-3.57; 1.18+/-0.93; and 2.11+/-1.60 (mean +/- SD). The apoptotic ratio in pilocytic astrocytomas was significantly higher than in other astrocytic tumors (fibrillary astrocytomas, p < 0.05; anaplastic astrocytomas and glioblastomas, p < 0.01). MIB-1 showed a significant negative correlation with apoptosis (p < 0.01). MIB- I and apoptosis showed significant negative and positive correlations with patient survival (p < 0.01). Mutations of p53 and PTEN show no correlation with survival and apoptotic ratio. The apoptotic ratio can clearly distinguish pilocytic astrocytomas from other tumors, and this biological feature may reflect less aggressive growth of pilocytic astrocytomas.
细胞增殖和细胞死亡在肿瘤组织中同时发生,肿瘤生长的程度反映了这些事件的净平衡。我们将细胞增殖、自发性细胞死亡以及肿瘤抑制蛋白的改变相互关联,并与原发性星形细胞瘤患者的生存率进行关联分析。在39例星形细胞瘤标本(6例毛细胞型星形细胞瘤、14例纤维型星形细胞瘤、9例间变性星形细胞瘤和10例胶质母细胞瘤)中,我们测定了MIB-1标记指数、经形态学确认的缺口末端标记法测定的凋亡率、p53标记指数以及p53或PTEN突变的存在情况。毛细胞型星形细胞瘤、纤维型星形细胞瘤、间变性星形细胞瘤和胶质母细胞瘤的MIB-1标记指数分别为0.30±0.32;1.84±1.87;19.3±6.42;和28.0±14.5(平均值±标准差)。相应的凋亡率分别为17.9±5.16;3.96±3.57;1.18±0.93;和2.11±1.60(平均值±标准差)。毛细胞型星形细胞瘤的凋亡率显著高于其他星形细胞瘤(纤维型星形细胞瘤,p<0.05;间变性星形细胞瘤和胶质母细胞瘤,p<0.01)。MIB-1与凋亡呈显著负相关(p<0.01)。MIB-1和凋亡与患者生存率呈显著负相关和正相关(p<0.01)。p53和PTEN的突变与生存率和凋亡率无关。凋亡率可以清楚地将毛细胞型星形细胞瘤与其他肿瘤区分开来,这一生物学特征可能反映了毛细胞型星形细胞瘤生长侵袭性较低。