TP53和MDM2基因分型与铂类治疗的头颈癌患者临床结局的相关性：超过10年的随访研究

Correlation of TP53 and MDM2 genotypes and clinical outcome in platinum-treated head and neck cancer patients with more than 10 years' follow-up.

作者信息

Vivenza Daniela, Monteverde Martino, Lattanzio Laura, Tonissi Federica, Astesana Valentina, Denaro Nerina, Comino Alberto, Russi Elvio, Lo Nigro Cristiana, Merlano Marco

机构信息

Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, Cuneo - Italy.

Medical Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, Cuneo - Italy.

出版信息

Int J Biol Markers. 2016 May 28;31(2):e183-92. doi: 10.5301/jbm.5000192.

DOI:10.5301/jbm.5000192

PMID:26916894

Abstract

PURPOSE

Adequate biomarkers are still required to optimize therapy in patients with locally advanced head and neck squamous carcinomas (HNSCC) treated with chemoradiotherapy (CRT).

METHODS

We updated the follow-up of 66 HNSCC patients treated with CRT we described more than 10 years ago, focusing on SNP Arg/Pro (R/P) at codon 72 and somatic mutations in TP53 and on SNP309 in the MDM2 gene.

RESULTS

In wild-type TP53 cases, overall survival (OS) was longer in 72RR and less favorable in 72PP (p = 0.005); when TP53 was mutated, OS was longest in 72PP and less favorable in 72RR and 72RP (p = 0.058). Median OS was significantly shorter in patients with MDM2 SNP309 GG or GT genotypes compared with the TT genotype (p = 0.002).

CONCLUSIONS

TP53 SNP72 may be useful in selecting patients for CRT, but has to be related to somatic TP53 mutations. The MDM2 SNP309, easily determined in peripheral blood, might be more convenient as a predictive biomarker.

摘要

目的

对于接受放化疗（CRT）的局部晚期头颈部鳞状细胞癌（HNSCC）患者，仍需要合适的生物标志物来优化治疗方案。

方法

我们对10多年前描述的66例接受CRT治疗的HNSCC患者进行了随访更新，重点关注第72密码子的单核苷酸多态性（SNP）精氨酸/脯氨酸（R/P）、TP53的体细胞突变以及MDM2基因中的SNP309。

结果

在野生型TP53病例中，72RR基因型患者的总生存期（OS）较长，72PP基因型患者的总生存期较差（p = 0.005）；当TP53发生突变时，72PP基因型患者的OS最长，72RR和72RP基因型患者的OS较差（p = 0.058）。与TT基因型相比，MDM2 SNP309 GG或GT基因型患者的中位OS显著缩短（p = 0.002）。