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p53突变是接受手术肿瘤消融的肝细胞癌患者生存的不良预后指标。

p53 mutation is a poor prognostic indicator for survival in patients with hepatocellular carcinoma undergoing surgical tumour ablation.

作者信息

Honda K, Sbisà E, Tullo A, Papeo P A, Saccone C, Poole S, Pignatelli M, Mitry R R, Ding S, Isla A, Davies A, Habib N A

机构信息

Department of Surgery, Hammersmith Hospital, RPMS, London, UK.

出版信息

Br J Cancer. 1998 Mar;77(5):776-82. doi: 10.1038/bjc.1998.126.

Abstract

Forty-two patients with hepatocellular carcinoma (HCC) were resected and their tumours were analysed for p53 mutations by GC-clamped denaturing gradient gel electrophoresis (DGGE), single-strand conformation polymorphism (SSCP) and gene sequencing. All the exons have been analysed in this study. Eight of 12 HCCs with cirrhosis due to viral hepatitis and the two patients with sarcomatoid changes displayed p53 mutations. In contrast, no mutation was observed in the fibrolamellar variant (n = 9), non-cirrhotics (n = 13) and alcoholic cirrhosis (n = 6). The mutations observed were in exons 5-8. Two mutations were observed in codons 136 and 213 as well as a T insertion between residues 156 and 157 (exon 5) and these are reported for the first time in HCC. Likewise, the silent mutation polymorphism in codon 213 was noticed in 3 of the 42 patients. Survival analysis of these patients after surgery showed the mean and median survival in patients with wild-type p53 to be 60 and 43 months respectively. In the group with p53 mutations, the mean and median survival was 15 and 12 months. The difference was statistically significant (P= 0.003).

摘要

42例肝细胞癌(HCC)患者接受了手术切除,并通过GC夹变性梯度凝胶电泳(DGGE)、单链构象多态性(SSCP)和基因测序分析其肿瘤的p53突变情况。本研究分析了所有外显子。12例因病毒性肝炎导致肝硬化的HCC患者中有8例以及2例出现肉瘤样改变的患者显示p53突变。相比之下,在纤维板层样变体(n = 9)、非肝硬化患者(n = 13)和酒精性肝硬化患者(n = 6)中未观察到突变。观察到的突变位于外显子5 - 8。在密码子136和213处观察到两个突变,以及在第156和157位残基之间(外显子5)有一个T插入,这些在HCC中均为首次报道。同样,在42例患者中有3例注意到密码子213处的沉默突变多态性。对这些患者术后的生存分析显示,p53野生型患者的平均生存时间和中位生存时间分别为60个月和43个月。在p53突变组中,平均生存时间和中位生存时间分别为15个月和12个月。差异具有统计学意义(P = 0.003)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dbf/2149958/9d732d7cb786/brjcancer00081-0099-a.jpg

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