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

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机构: [1]Department of Gynaecologic Oncology, Sichuan Cancer Hospital, Chengdu, Sichuan, PR China [2]Department of Biochemistry & Molecular Biology, Sichuan Cancer Institute, Chengdu, Sichuan, PR China [3]Graduate School, Guangxi Medical University, Nanning, Guangxi, PR China [4]Graduate School, Luzhou Medical College, Luzhou, Sichuan, PR China [5]Department of Ultrasound, Sichuan Cancer Hospital, Chengdu, Sichuan, PR China
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关键词: Ovarian cancer TP53 K351N mutation Neoadjuvant chemotherapy

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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. (C) 2014 Elsevier Inc. All rights reserved.

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出版当年[2014]版:
大类 | 2 区 医学
小类 | 2 区 妇产科学 3 区 肿瘤学
最新[2023]版:
大类 | 2 区 医学
小类 | 1 区 妇产科学 2 区 肿瘤学
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出版当年[2014]版:
Q1 OBSTETRICS & GYNECOLOGY Q2 ONCOLOGY
最新[2023]版:
Q1 OBSTETRICS & GYNECOLOGY Q1 ONCOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2014版] 出版当年五年平均 出版前一年[2013版] 出版后一年[2015版]

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第一作者机构: [1]Department of Gynaecologic Oncology, Sichuan Cancer Hospital, Chengdu, Sichuan, PR China [3]Graduate School, Guangxi Medical University, Nanning, Guangxi, PR China [4]Graduate School, Luzhou Medical College, Luzhou, Sichuan, PR China
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通讯机构: [2]Department of Biochemistry & Molecular Biology, Sichuan Cancer Institute, Chengdu, Sichuan, PR China [*1]Department of Biochemistry & Molecular Biology, Sichuan Cancer Institute No. 55, Section 4, South People's Road, Chengdu 610041, Sichuan, PR China
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