乳腺癌患者外周血DNA p53基因突变的检测及其与预后关系的研究

Peripheral blood mutated p53 DNA and its clinical value in human breast cancer

目的 探讨乳腺癌患者外周血中DNAp5 3基因突变与预后的关系。方法 对 12 6例乳腺癌患者和 92例正常对照者血浆DNA含量进行检测。外周血浆中DNA由Qiagen纯化柱纯化 ,组织标本DNA抽提方法参照非有机化方法。应用PCR SSCP方法检测DNA中p5 3基因 5 ,6 ,7,8外显子点突变。结果 健康妇女外周血中DNA的平均值为 2 1ng/ml,而乳腺癌患者为 2 11ng/ml(P <0 .0 1)。12 6例乳腺癌患者中有 4 6例 (35 .6 % )原发瘤中检出p5 3突变 ,其中 30例 (6 5 .2 % )患者外周血DNA中检出p5 3基因突变。乳腺癌患者外周血中DNAp5 3基因突变与临床分期、肿瘤大小、淋巴结转移情况和雌激素受体状况密切相关 (P <0 .0 5 )。肿瘤原发灶与外周血中均检出DNAp5 3基因突变者预后较差 ,2 2例发生复发或转移的患者中 ,有 13例 (5 9.0 % )外周血中检出DNAp5 3基因突变。结论 乳腺癌患者外周血中DNAp5 3基因的突变 ,可作为一种预后指标和提示肿瘤早期复发和远处转移的预后因子。

Objective To evaluate the clinical value of mutated p53 in the peripheral blood of breast cancer patients. Methods Plasma DNA of 126 breast cancer patients and 92 healthy women was examined. DNA extraction from the tumor and tissue samples was performed by a nonorganic method. Plasma DNA was purified on Qiagen columns. PCR SSCP analysis was performed to examine the point mutations in the conserved exons 5,6,7 and 8 of TP53. Results The mean concentration of plasma DNA was 21 ng/ml in healthy women and 211 ng/ml in patients with breast cancer ( P <0.01 ). p53 mutations in the primary tumor were detected in 46 of 126 ( 36.5% ) breast cancer patients. Of these 46 patients, 30 (65.1%) were also found to have p53 mutations in their plasma DNA. p53 mutation in plasma DNA was closely correlated with clinical stage, tumor size, lymphnode (LN) metastasis and estrogen receptor status ( P <0.05) . Survival of the patients with both primary tumor and plasma p53 mutations was the worst. Thirteen of the 22 (59.0%) patients with recurrence and/or metastasis had detectable p53 mutations in their plasma DNA. Conclusion p53 mutations in plasma DNA may be a useful prognostic factor and an early marker of recurrence or distant metastasis in breast cancer.