Wang Y, Helland A, Holm R, Skomedal H, Abeler V M, Danielsen H E, Tropé C G, Børresen-Dale A-L, Kristensen G B
Department of Gynecologic Oncology, The Norwegian Radium Hospital, Oslo N-0310, Norway.
Br J Cancer. 2004 Feb 9;90(3):678-85. doi: 10.1038/sj.bjc.6601537.
We conducted the present study to evaluate the frequency and prognostic importance on long-term survival of TP53 mutations and TP53 protein accumulation in a cohort of 178 patients with early-stage ovarian carcinomas. TP53 mutations scored as aberrant temporal temperature gradient gel electrophoresis pattern from all exons were observed in 39.9% of the tumours. Full screening of exons 5-8, followed by sequencing, was successful in 135 cases, and 48 mutations altering the protein were detected in 39 cases (28.9%). TP53 mutations were slightly less common in the Federation of Gynecologists and Obstetricians stage IA than in IB/IC (P=0.05). No significant correlations with histological type, grade of differentiation, DNA ploidy status or age at diagnosis were found. TP53 protein accumulation analysed by immunohistochemistry was found in 32.6% of all tumours, and was a poor predictor of TP53 mutations with 56.4% sensitivity, 77.1% specificity, 50% positive predictive value and 81.3% negative predictive value. Neither TP53 mutations nor TP53 protein accumulation influenced the prognosis significantly in this group of patients.
我们开展了本研究，以评估178例早期卵巢癌患者队列中TP53突变和TP53蛋白积聚的频率及其对长期生存的预后重要性。通过异常的时间温度梯度凝胶电泳模式对所有外显子进行评分，发现39.9%的肿瘤存在TP53突变。对135例患者成功进行了外显子5至8的全面筛查并测序，在39例患者（28.9%）中检测到48个改变蛋白的突变。在国际妇产科联合会IA期，TP53突变的发生率略低于IB/IC期（P = 0.05）。未发现与组织学类型、分化程度、DNA倍体状态或诊断时年龄存在显著相关性。通过免疫组织化学分析发现，32.6%的肿瘤存在TP53蛋白积聚，其对TP53突变的预测能力较差，敏感性为56.4%，特异性为77.1%，阳性预测值为50%，阴性预测值为81.3%。在这组患者中，TP53突变和TP53蛋白积聚均未对预后产生显著影响。
