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IDH 野生型组织学定义的胶质母细胞瘤患者中 TP53 突变与生存的关系。

TP53 mutations and survival in patients with histologically defined Glioblastoma, IDH-wildtype.

机构信息

Nervous System Medical Oncology Department, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.

Nervous System Medical Oncology Department, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.

出版信息

Pathol Res Pract. 2024 Oct;262:155516. doi: 10.1016/j.prp.2024.155516. Epub 2024 Aug 8.

Abstract

BACKGROUND

Mutations of the TP53 oncosuppressor gene are frequent events in patients with malignant tumors including IDH-wildtype GBM (GBM IDH wt). However, the effective impact of TP53 mutations on prognosis has been poorly evaluated.

METHODS

We performed a retrospective study investigating the impact of TP53 mutations on patients with GBM IDH wt. Only patients with PS=0-1, treated with temozolomide concurrent with and adjuvant to radiotherapy, and younger than 70 years assessed with NGS were included in the analysis.

RESULTS

97 GBM IDH wt have been selected. The median follow-up was 34.5 months (95 %CI, 30.6 - NA). Overall, 20 patients (19.4 %) presented a TP53 mutation. There were no significant differences in terms of TERT mutation (75 % vs 79.2 %) between TP53 mutated and TP53 wild-type (wt) patients. We detected 6 TP53 mutations not previously described within GBM IDH wt patients. The overall survival (OS) did not significantly differ between TP53 mutated and wt patients (HR 0.69, 95 %CI 0.37-1.27, p = 0.24). Considering only patients with an OS longer than 36 months (n = 10), the presence of a TP53 mutation was significantly associated with prolonged survival (45.6 months vs Not Reached, p = 0.037).

CONCLUSION

The presence of a TP53 mutation does not appear to be correlated with overall survival in this patient cohort. While there is an association with survival for patients with an OS of 36 months or longer, the number of patients is low and there is no available evidence correlating TP53 mutations to long-term survivors.

摘要

背景

TP53 抑癌基因突变在包括 IDH 野生型 GBM(GBM IDHwt)在内的恶性肿瘤患者中经常发生。然而,TP53 突变对预后的有效影响尚未得到充分评估。

方法

我们进行了一项回顾性研究,调查了 TP53 突变对 GBM IDHwt 患者的影响。仅纳入 PS=0-1、接受替莫唑胺同步放化疗且年龄小于 70 岁的患者进行 NGS 检测,分析其结果。

结果

共纳入 97 例 GBM IDHwt 患者。中位随访时间为 34.5 个月(95%CI,30.6-Na)。总体而言,20 例(19.4%)患者存在 TP53 突变。TP53 突变和 TP53 野生型(wt)患者的 TERT 突变率(75% vs 79.2%)无显著差异。我们在 GBM IDHwt 患者中检测到 6 种先前未描述的 TP53 突变。TP53 突变和 wt 患者的总生存期(OS)无显著差异(HR 0.69,95%CI 0.37-1.27,p=0.24)。仅考虑 OS 长于 36 个月的患者(n=10),TP53 突变的存在与延长的生存时间显著相关(45.6 个月 vs 未达到,p=0.037)。

结论

在该患者队列中,TP53 突变的存在似乎与总体生存无关。虽然 OS 为 36 个月或更长的患者的生存与 TP53 突变相关,但患者数量较少,且目前尚无证据表明 TP53 突变与长期生存者相关。

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