晚期卵巢癌患者新辅助化疗后与 TP53 K351N 突变相关的铂类耐药。

TP53 K351N mutation-associated platinum resistance after neoadjuvant chemotherapy in patients with advanced ovarian cancer.

机构信息

Department of Gynaecologic Oncology, Sichuan Cancer Hospital, Chengdu, Sichuan, PR China; Graduate School, Guangxi Medical University, Nanning, Guangxi, PR China; Graduate School, Luzhou Medical College, Luzhou, Sichuan, PR China.

Department of Gynaecologic Oncology, Sichuan Cancer Hospital, Chengdu, Sichuan, PR China.

出版信息

Gynecol Oncol. 2014 Mar;132(3):752-7. doi: 10.1016/j.ygyno.2014.01.028. Epub 2014 Jan 23.

DOI:10.1016/j.ygyno.2014.01.028

PMID:24463159

Abstract

OBJECTIVE

TP53 K351N mutation is associated with acquired cisplatin resistance in ovarian cancer cells following exposure to cisplatin. We investigated the effect of TP53 K351N mutation on outcome in patients with epithelial ovarian cancer (EOC) who received platinum-based chemotherapy.

METHODS

We assessed TP53 K351N mutations by allele specific real-time PCR (AS-PCR) and DNA sequencing in tumor samples of 153 patients with stage IIIC/IV EOC. Clinicopathologic and follow-up data were collected by a retrospective chart review.

RESULTS

TP53 K351N mutations were detected in 8 (11.27%) of 71 patients who underwent neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) but not in 82 patients who underwent primary debulking surgery (PDS) (P<0.01). In patients with relapse within 6 months, the relapse rate was 14 (19.72%) of 71 patients for NACT-IDS compared to 15 (18.29%) of 82 patients for PDS (P=0.49), and TP53 K351N mutation was observed in 8 of NACT-IDS 14 patients (57.14% P<0.01). In the patients retreated at first recurrence within 6 months, 7 with TP53 K351N mutation of 14 NACT-IDS patients exhibited progression of disease, compared to 2 of PDS 15 patients (50.00% vs. 13.33%, P=0.04). The median disease-free survival (DFS) for NACT-IDS was 13.0 months compared to 15.0 months for PDS (P=0.02). In multivariate analysis, TP53 K351N mutation is an independent factor for shorter DFS in the patients who underwent NACT-IDS (HR=19.05; P=0.01).

CONCLUSIONS

TP53 K351N mutation may be associated with induction of platinum resistance after NACT in advanced EOC.

摘要

目的

TP53 K351N 突变与卵巢癌细胞在顺铂暴露后获得顺铂耐药有关。我们研究了 TP53 K351N 突变对接受铂类化疗的上皮性卵巢癌（EOC）患者结局的影响。

方法

我们通过等位基因特异性实时 PCR（AS-PCR）和 DNA 测序评估了 153 例 IIIC/IV 期 EOC 患者肿瘤样本中的 TP53 K351N 突变。通过回顾性病历审查收集临床病理和随访数据。

结果

8 例（11.27%）接受新辅助化疗联合间隔减瘤术（NACT-IDS）的患者中检测到 TP53 K351N 突变，但 82 例接受直接减瘤术（PDS）的患者中未检测到（P<0.01）。在 6 个月内复发的患者中，NACT-IDS 组 71 例患者中有 14 例（19.72%）复发，PDS 组 82 例患者中有 15 例（18.29%）复发（P=0.49），NACT-IDS 组 14 例患者中有 8 例（57.14%）检测到 TP53 K351N 突变（P<0.01）。在首次复发后 6 个月内再次治疗的患者中，NACT-IDS 组 14 例患者中有 7 例（50.00%）出现疾病进展，而 PDS 组 15 例患者中有 2 例（13.33%）出现疾病进展（P=0.04）。NACT-IDS 组的无疾病进展生存期（DFS）中位数为 13.0 个月，而 PDS 组为 15.0 个月（P=0.02）。多因素分析显示，TP53 K351N 突变是 NACT-IDS 患者 DFS 较短的独立因素（HR=19.05；P=0.01）。