Bosari S, Viale G, Bossi P, Maggioni M, Coggi G, Murray J J, Lee A K
Department of Pathology, University of Milan School of Medicine, Italy.
J Natl Cancer Inst. 1994 May 4;86(9):681-7. doi: 10.1093/jnci/86.9.681.
Aberrations of the p53 gene (also known as TP53) frequently lead to the synthesis of mutant proteins that accumulate in the nuclei and/or cytoplasm of neoplastic cells. Intracellular p53 protein accumulation may be an unfavorable prognostic parameter in breast, lung, ovarian, gastric, and colorectal cancers. Specific classes of p53 gene mutations, assayed by characteristic subcellular p53 protein accumulation patterns, may be useful prognostic indicators.
The prognostic value of nuclear and cytoplasmic p53 protein accumulation in the tumor cells of patients with colorectal carcinoma was studied.
Antibodies PAb 1801 and CM1 were used for immunocytochemical assay of nuclear and cytoplasmic p53 protein accumulation in a retrospective series of colorectal carcinoma samples obtained from 206 patients who were followed for at least 5 years. Results were correlated with the following clinicopathologic parameters: patient sex and age; tumor site, stage, and grade; and DNA ploidy status of the tumors. Overall survival and disease-free survival were analyzed with the Kaplan-Meier method. Differences in distributions were analyzed using the Mantel-Cox method. Multivariate analysis was performed with the Cox proportional hazards model.
Immunostaining with PAb 1801 revealed nuclear p53 accumulation in 46% (95) of 206 cases, whereas CM1 immunostaining of 197 cases showed nuclear and cytoplasmic p53 accumulation in 33% (65 cases) and 50% (99 cases) of the cases, respectively. In univariate analysis, both nuclear p53PAb 1801 and cytoplasmic p53CM1 protein accumulations were significantly associated with poor overall survival (P = .0198 and P = .0017, respectively) and with disease-free survival (P = .004 and P = .0016, respectively). When patients were analyzed according to site of their tumors, nuclear p53PAb 1801 protein accumulation was statistically significant only in the right colon (P = .027), whereas cytoplasmic p53CM1 protein accumulation was statistically significant in the left colon and rectum (P = .0016). In multivariate analysis, only cytoplasmic p53CM1 protein accumulation was associated with poor overall survival and with disease-free survival (P = .006 and P = .002, respectively). With the addition of DNA ploidy status, however, cytoplasmic p53CM1 protein accumulation remained significant only for disease-free survival (P = .035). In patients with tumors of the left colon and rectum, cytoplasmic p53CM1 protein accumulation was the most significant prognostic indicator for overall survival (P = .007) and disease-free survival (P = .002) after disease stage.
Cytoplasmic p53CM1 protein accumulation, but not nuclear p53PAb 1801 protein accumulation, is an independent prognostic parameter in patients with colorectal carcinomas.
Cytoplasmic p53CM1 accumulation may be a useful indicator of patients at high risk for disease recurrence who may benefit from aggressive adjuvant therapy.
p53基因（也称为TP53）异常常导致突变蛋白的合成，这些蛋白积聚在肿瘤细胞的细胞核和/或细胞质中。细胞内p53蛋白积聚可能是乳腺癌、肺癌、卵巢癌、胃癌和结直肠癌中一个不利的预后参数。通过特征性亚细胞p53蛋白积聚模式检测的特定类型的p53基因突变，可能是有用的预后指标。
研究结直肠癌患者肿瘤细胞中细胞核和细胞质p53蛋白积聚的预后价值。
使用抗体PAb 1801和CM1对从206例随访至少5年的结直肠癌样本中获取的回顾性系列样本进行免疫细胞化学检测，以检测细胞核和细胞质p53蛋白积聚情况。结果与以下临床病理参数相关：患者性别和年龄；肿瘤部位、分期和分级；以及肿瘤的DNA倍体状态。采用Kaplan-Meier法分析总生存期和无病生存期。使用Mantel-Cox法分析分布差异。采用Cox比例风险模型进行多变量分析。（此处英文原文有误，应是“Multivariate analysis was performed with the Cox proportional hazards model.”）
PAb 1801免疫染色显示206例中有46%（95例）细胞核p53积聚，而197例的CM1免疫染色分别显示33%（65例）细胞核和50%（99例）细胞质p53积聚。在单变量分析中，细胞核p53PAb 1801和细胞质p53CM1蛋白积聚均与总生存期差显著相关（分别为P = 0.0198和P = 0.0017）以及与无病生存期差显著相关（分别为P = 0.004和P = 0.0016）。当根据肿瘤部位分析患者时，细胞核p53PAb 1801蛋白积聚仅在右半结肠有统计学意义（P = 0.027），而细胞质p53CM1蛋白积聚在左半结肠和直肠有统计学意义（P = 0.0016）。在多变量分析中，只有细胞质p53CM1蛋白积聚与总生存期差和无病生存期差相关（分别为P = 0.006和P = 0.002）。然而，加入DNA倍体状态后，细胞质pCM1蛋白积聚仅对无病生存期仍有显著意义（P = 0.035）。在左半结肠和直肠肿瘤患者中，细胞质p53CM1蛋白积聚是疾病分期后总生存期（P = 0.007）和无病生存期（P = 0.002）最显著的预后指标。
细胞质p53CM1蛋白积聚而非细胞核p53PAb 1801蛋白积聚是结直肠癌患者的一个独立预后参数。
细胞质p53CM积聚可能是疾病复发高危患者的一个有用指标，这些患者可能从积极的辅助治疗中获益。
