Regidor P A, Regidor M, Callies R, Schindler A E
Department of Gynecology, University of Essen, Germany.
Eur J Gynaecol Oncol. 1996;17(3):192-9.
Mutations of the tumor suppressor gene p53 are common in multiple cancer forms, including breast cancer. Data are available that suggest, that the loss of the wild type form of p53 and the appearance of the mutant forms of p53 are correlated with a poorer overall survival rate in patients with breast cancer. The accumulation of the mutant forms of p53 in the cytoplasmatic rooms of the tumor cells leads to the production of human auto-antibodies against these mutant p53 proteins. Therefore, the aim of this study was to analyse and quantify the levels of serum auto-antibodies against p53 protein in patients with an intact immunological system having an active and new recurrence of breast cancer and to compare the obtained results with the recurrence free interval and with established prognostic parameters at the time of first diagnosis, to see if patients with a positive p53 auto-antibody status had a poorer prognosis than those who were p53 auto-antibody positive.
The ser of 61 patients with breast cancer, who experienced a new, clinical and biophysically identified local or distant recurrence and that showed an intact immunological system were analysed with an ELISA assay of Dianova to determine the concentration of auto-antibodies against mutant p53.
14.5% of the patients showed a positive p53 auto-antibody serum status. The recurrence free interval between the p53 auto-antibody positive and negative patients was almost the same: 4.12 years for the p53 auto-antibody positive patients versus 3.72 years for the p53 auto-antibody negative patients (independent t-test value = 0.224 and p value = 0.824; statistically not a significant difference). When comparing the p53 auto-antibody status with established prognostic parameters we could only find a statistically significant correlation with tumor size. No correlations were obtained when comparing the p53 auto-antibody status with the N- and M status, the ER- and PR status, the menopausal status and the cathepsin-D status.
We were able to demonstrate that the expression of serum auto-antibodies against mutant p53 can not be used as a prognostic parameter in patients with breast cancer as the recurrence free interval between the p53 auto-antibody positive and negative patients did not differ. The determination of the auto-antibodies against p53, though easy to perform, is therefore not a test that helps clinicians in their treatment options, but it remains a useful test for the description of the biological mechanisms of breast cancer.
肿瘤抑制基因p53的突变在包括乳腺癌在内的多种癌症形式中很常见。现有数据表明,野生型p53的缺失和p53突变形式的出现与乳腺癌患者较差的总生存率相关。肿瘤细胞胞质中p53突变形式的积累导致针对这些突变p53蛋白的人类自身抗体的产生。因此,本研究的目的是分析和量化免疫系统健全且患有活跃新发复发性乳腺癌患者血清中针对p53蛋白的自身抗体水平,并将所得结果与无复发生存期以及首次诊断时既定的预后参数进行比较,以查看p53自身抗体状态为阳性的患者预后是否比p53自身抗体为阴性的患者更差。
对61例乳腺癌患者的血清进行分析,这些患者经历了新的、临床和生物物理学确定的局部或远处复发且免疫系统健全,采用Dianova的ELISA检测法测定针对突变p53的自身抗体浓度。
14.5%的患者p53自身抗体血清状态为阳性。p53自身抗体阳性和阴性患者的无复发生存期几乎相同:p53自身抗体阳性患者为4.12年,p53自身抗体阴性患者为3.72年(独立t检验值 = 0.224,p值 = 0.824;统计学上无显著差异)。当将p53自身抗体状态与既定的预后参数进行比较时,我们仅发现与肿瘤大小存在统计学上的显著相关性。将p53自身抗体状态与N和M状态、ER和PR状态、绝经状态以及组织蛋白酶D状态进行比较时,未发现相关性。
我们能够证明,针对突变p53的血清自身抗体表达不能用作乳腺癌患者的预后参数,因为p53自身抗体阳性和阴性患者的无复发生存期没有差异。因此,针对p53的自身抗体检测虽然易于进行,但并不是一种有助于临床医生选择治疗方案的检测方法,但它仍然是描述乳腺癌生物学机制的一种有用检测方法。