Psyrri A, Kountourakis P, Yu Z, Papadimitriou C, Markakis S, Camp R L, Economopoulos T, Dimopoulos M A
Department of Medical Oncology, Yale Cancer Center, New Haven, CT 06520, USA. diamando.psyrri@ yale.edu
Ann Oncol. 2007 Apr;18(4):709-15. doi: 10.1093/annonc/mdl479. Epub 2007 Jan 13.
p53 protein is regarded as a valuable prognostic marker in cancer with a potential use as a molecular target. Here, we sought to determine the prognostic value of p53 in ovarian cancer using a novel method of compartmentalized in situ protein analysis.
A tissue array composed of 141 advanced stage ovarian cancers uniformly treated was constructed. For evaluation of p53 protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis (AQUA).
High nuclear p53 expression levels were associated with better outcome for overall survival (OS) (P = 0.0023) and disease-free survival (P = 0.0338) at 5-years. High cytoplasmic p53 expression levels were associated with better outcome for OS (P = 0.0002). In multivariable analysis, high nuclear and high cytoplasmic p53 level with International Federation of Gynecology and Obstetrics (FIGO) stage were the most significant predictor variables for OS and high nuclear p53 level with FIGO stage were the significant predictor variables for disease-free survival.
Assessment of the prognostic value of p53 protein levels using conventional immunohistochemistry is limited by the nonquantitative nature of the method. AQUA provides precise estimation of p53 protein levels and was able to elucidate the association of p53 protein levels and ovarian cancer prognosis.
p53蛋白被视为癌症中有价值的预后标志物,具有作为分子靶点的潜在用途。在此,我们试图采用一种新的分区原位蛋白质分析方法来确定p53在卵巢癌中的预后价值。
构建了一个由141例接受统一治疗的晚期卵巢癌组成的组织芯片。为评估p53蛋白表达,我们采用了基于免疫荧光的蛋白质分析自动原位定量测量方法(AQUA)。
5年时,高核p53表达水平与总生存期(OS)(P = 0.0023)和无病生存期(P = 0.0338)的较好预后相关。高细胞质p53表达水平与OS的较好预后相关(P = 0.0002)。在多变量分析中,高核和高细胞质p53水平与国际妇产科联盟(FIGO)分期是OS最显著的预测变量,高核p53水平与FIGO分期是无病生存期的显著预测变量。
使用传统免疫组织化学评估p53蛋白水平的预后价值受到该方法非定量性质的限制。AQUA可精确估计p53蛋白水平,并能够阐明p53蛋白水平与卵巢癌预后的关联。