Tullo A, D'Erchia A M, Honda K, Mitry R R, Kelly M D, Habib N A, Saccone C, Sbisà E
Centro di Studio sui Mitocondri e Metabolismo Energetico, Consiglio Nazionale delle Ricerche, Bari, Italy.
Clin Cancer Res. 1999 Nov;5(11):3523-8.
The presence and type of mutations of the p53 tumor suppressor gene were determined in 40 patients undergoing curative hepatic resection for metastatic colorectal carcinoma. This represents the largest series in the literature on the screening of p53 mutations for liver metastases. The analysis was performed in exons 5-9 by denaturing gradient gel electrophoresis followed by direct sequencing. Forty-five percent of tumors showed mutation in p53, and this was observed only in exons 5-8. Mutations at codon positions 167, 196, 204, 213, 245, 281, 282, 286, and 306; deletion of codon 251 and of the first nucleotide of codon 252; and Leu residue (CTC) insertion downstream codon 252 are reported for the first time in colorectal liver metastasis. Mutations at codon positions 163, 248, and 273 have been reported previously. Correlation of p53 status with clinical parameters showed that patients with mutated p53 had a statistically higher number of lesions when compared with patients with wild-type p53 (P<0.050). In particular, of patients with mutated p53, 41% had three or more metastases compared with 14% of patients with wild-type p53. Synchronous metastases were present in 70% of the patients with p53 mutations and in only 29% of patients with wild-type p53 (P<0.025). In addition, patients with p53 mutations are more likely to develop recurrence (73%) compared with patients with wild-type p53 (33%; P<0.001). Other factors considered, including preoperative carcinoembryonic antigen level, bilobar distribution, and size of the lesion(s), did not show significant correlation with p53 status. These results suggest that p53 status might be an important prognostic indicator to predict the pattern and likelihood of treatment failure after hepatic resection.
在40例接受转移性结直肠癌根治性肝切除术的患者中，确定了p53肿瘤抑制基因的突变情况及类型。这是文献中关于肝转移瘤p53突变筛查的最大样本系列研究。通过变性梯度凝胶电泳结合直接测序对第5至9外显子进行分析。45%的肿瘤显示p53突变，且仅在第5至8外显子中观察到。密码子位置167、196、204、213、245、281、282、286和306处的突变；密码子251及密码子252第一个核苷酸的缺失；以及密码子252下游亮氨酸残基（CTC）的插入，在结直肠癌肝转移中首次报道。密码子位置163、248和273处的突变先前已有报道。p53状态与临床参数的相关性分析显示，与野生型p53患者相比，p53突变患者的病灶数量在统计学上显著更多（P<0.050）。特别是，p53突变患者中有41%有三个或更多转移灶，而野生型p53患者中这一比例为14%。70%的p53突变患者存在同时性转移，而野生型p53患者中仅为29%（P<0.025）。此外，与野生型p53患者（33%；P<0.001）相比，p53突变患者更易发生复发（73%）。所考虑的其他因素，包括术前癌胚抗原水平、双叶分布及病灶大小，与p53状态均无显著相关性。这些结果表明，p53状态可能是预测肝切除术后治疗失败模式及可能性的重要预后指标。
