Manne U, Weiss H L, Myers R B, Danner O K, Moron C, Srivastava S, Grizzle W E
Department of Pathology, University of Alabama at Birmingham, 35294, USA.
Cancer. 1998 Dec 15;83(12):2456-67. doi: 10.1002/(sici)1097-0142(19981215)83:12<2456::aid-cncr8>3.0.co;2-5.
Although several studies have been conducted to examine the role of p53 genetic abnormalities and their prognostic value in colorectal carcinoma, the incidence of nuclear accumulation of p53 and the prognostic importance of nuclear accumulation of p53 in African-American and white patients have not been investigated separately. Therefore, the authors evaluated the prognostic significance of p53 nuclear accumulation in these two racial groups.
Nuclear accumulation of p53 was evaluated immunohistochemically in archival tissue specimens from 204 African-American and 300 white patients with primary colorectal adenocarcinomas who had undergone surgery. Survival times from colorectal adenocarcinoma were analyzed using Kaplan-Meier survival estimates and the Cox proportional hazards model for nuclear accumulation of p53 with adjustments for other confounding demographic and clinical variables.
Approximately equivalent proportions of distal (54%) and proximal adenocarcinomas (47%) were positive for nuclear accumulation of p53 in African-American patients. In contrast, distal colorectal adenocarcinomas from white patients more frequently were positive for nuclear accumulation of p53 than adenocarcinomas of the proximal colon (63% vs. 38%, respectively). Nuclear accumulation of p53 was found to be a strong predictor of poor survival in white patients (hazard ratio = 6.77; P = 0.0001) but not in African-American patients with primary adenocarcinomas of the proximal colon. Nuclear accumulation of p53 was not of prognostic value in patients of either race with primary adenocarcinomas of the distal colorectum.
Nuclear accumulation of p53 is a valuable indicator of poor prognosis only for white patients with adenocarcinomas of the proximal colon. The current study also suggests that the role of p53 dysregulation in colorectal adenocarcinomas may vary with the anatomic location of the tumor and the race of the patient. These findings suggest that the demographic characteristics of patients should be considered in the evaluation of prognostic markers of colorectal neoplasia.
尽管已经开展了多项研究来探讨p53基因异常在结直肠癌中的作用及其预后价值，但p53核积聚的发生率以及p53核积聚在非裔美国人和白人患者中的预后重要性尚未分别进行研究。因此，作者评估了这两个种族群体中p53核积聚的预后意义。
采用免疫组织化学方法评估204例接受手术的非裔美国原发性结直肠腺癌患者和300例白人原发性结直肠腺癌患者存档组织标本中p53的核积聚情况。使用Kaplan-Meier生存估计和Cox比例风险模型分析结直肠腺癌的生存时间，对p53核积聚进行分析，并对其他混杂的人口统计学和临床变量进行调整。
在非裔美国患者中，远端（54%）和近端腺癌（47%）中p53核积聚阳性的比例大致相当。相比之下，白人患者的远端结直肠腺癌p53核积聚阳性的频率高于近端结肠癌（分别为63%和38%）。发现p53核积聚是白人患者生存不良的有力预测指标（风险比=6.77；P=0.0001），但在患有近端结肠原发性腺癌的非裔美国患者中并非如此。p53核积聚对任何一个种族的远端结直肠癌原发性腺癌患者均无预后价值。
p53核积聚仅是近端结肠腺癌白人患者预后不良的一个有价值指标。当前研究还表明，p53失调在结直肠腺癌中的作用可能因肿瘤的解剖位置和患者的种族而异。这些发现提示，在评估结直肠肿瘤的预后标志物时应考虑患者的人口统计学特征。
