Qin Lun-Xiu, Tang Zhao-You, Ma Zeng-Chen, Wu Zhi-Quan, Zhou Xin-Da, Ye Qing-Hai, Ji Yuan, Huang Li-Wen, Jia Hu-Liang, Sun Hui-Chuan, Wang Lu
Liver Cancer Institute & Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai 200032, China.
World J Gastroenterol. 2002 Jun;8(3):459-63. doi: 10.3748/wjg.v8.i3.459.
To confirm if p53 mutation could be a routine predictive marker for the prognosis of hepatocellular carcinoma (HCC) patients.
Two hundreds and forty-four formalin-fixed paraffin-embedded tumor samples of the patients with HCC receiving liver resection were detected for nuclear accumulation of p53. The percent of P53 immunoreactive tumor cells was scored as 0 to 3+ in P53 positive region (<10% -, 10-30% +, 31-50% ++, >50% +++). Proliferating cell nuclear antigen (PCNA) and some clinicopathological characteristics, including patients' sex, preoperative serum AFP level, tumor size, capsule, vascular invasion (both visual and microscopic), and Edmondson grade were also evaluated.
In univariate COX harzard regression model analysis, tumor size, capsule status, vascular invasion, and p53 expression were independent factors that were closely related to the overall survival (OS) rates of HCC patients. The survival rates of patients with 3+ for P53 expression were much lower than those with 2+ or + for P53 expression. Only vascular invasion (P<0.05) and capsule (P<0.01) were closely related to the disease-free survival (DFS) of HCC patients. In multivariate analysis, p53 overexpression (RI 0.5456, P<0.01) was the most significant factor associated with the OS rates of patients after HCC resection, while tumor size (RI 0.5209, P<0.01), vascular invasion (RI 0.5271, P<0.01) and capsule (RI-0.8691, P<0.01) were also related to the OS. However, only tumor capsular status was an independent predictive factor (P<0.05) for the DFS. No significant prognostic value was found in PCNA-LI, Edmondson's grade, patients' sex and preoperative serum AFP level.
Accumulation of p53 expression, as well as tumor size, capsule and vascular invasion, could be valuable markers for predicting the prognosis of HCC patients after resection. The quantitative immunohistochemical scoring for P53 nuclear accumulation might be more valuable for predicting prognosis of patients after HCC resection than the common qualitative analysis.
确认p53突变是否可作为肝细胞癌(HCC)患者预后的常规预测标志物。
对244例接受肝切除术的HCC患者的福尔马林固定石蜡包埋肿瘤样本进行p53核聚集检测。在p53阳性区域(<10%为-,10%-30%为+,31%-50%为++,>50%为+++),将P53免疫反应性肿瘤细胞百分比评分为0至3+。还评估了增殖细胞核抗原(PCNA)以及一些临床病理特征,包括患者性别、术前血清甲胎蛋白水平、肿瘤大小、包膜、血管侵犯(肉眼和显微镜下)以及Edmondson分级。
在单因素COX风险回归模型分析中,肿瘤大小、包膜状态、血管侵犯和p53表达是与HCC患者总生存率(OS)密切相关的独立因素。P53表达为3+的患者生存率远低于P53表达为2+或+的患者。仅血管侵犯(P<0.05)和包膜(P<0.01)与HCC患者无病生存率(DFS)密切相关。在多因素分析中,p53过表达(相对指数0.5456,P<0.01)是与HCC切除术后患者OS率相关的最显著因素,而肿瘤大小(相对指数0.5209,P<0.01)、血管侵犯(相对指数0.5271,P<0.01)和包膜(相对指数-0.8691,P<0.01)也与OS相关。然而,只有肿瘤包膜状态是DFS的独立预测因素(P<0.05)。在PCNA-LI、Edmondson分级、患者性别和术前血清甲胎蛋白水平方面未发现显著的预后价值。
p53表达的积累以及肿瘤大小、包膜和血管侵犯可能是预测HCC患者切除术后预后的有价值标志物。P53核积累的定量免疫组化评分可能比普通定性分析对预测HCC切除术后患者的预后更有价值。