Prognostic significance of PIK3CA mutation in stage IIB to IVA cervical cancers treated by concurrent chemoradiotherapy with weekly cisplatin.
Prognostic significance of PIK3CA mutation in stage IIB to IVA cervical cancers treated by concurrent chemoradiotherapy with weekly cisplatin.
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DOI：
10.1097/md.0000000000011392
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发表时间：
2018-08
期刊：
影响因子：
1.6
通讯作者：
Satoh T
中科院分区：
文献类型：
--
作者：
Lachkar B;Minaguchi T;Akiyama A;Liu S;Zhang S;Xu C;Shikama A;Tasaka N;Sakurai M;Nakao S;Ochi H;Yoshikawa H;Satoh T
局部晚期宫颈癌的标准治疗是基于顺铂的同步放化疗（CCRT）。虽然已知活化的pi3激酶/Akt通路参与顺铂耐药和放射耐药，但迄今为止，只有少数研究报道了PIK3CA基因突变状态与CCRT在该疾病中的预后之间的显著关联。本研究的目的是阐明PIK3CA突变状态在CCRT治疗宫颈癌中的预后意义。我们分析了59例IIB至IVA期宫颈癌患者的PIK3CA突变，这些患者主要接受每周一次顺铂的CCRT治疗，治疗前使用福尔马林固定石蜡包埋活检标本。59例患者中57例（97%）为局部晚期癌症，分期为IIIA至IVA期。根据PIK3CA突变状态，回顾性比较临床病理资料和患者生存率。59例患者中有7例（12%）发现PIK3CA突变。PIK3CA突变状态在临床病理特征上无明显差异。携带野生型PIK3CA的患者与携带突变型PIK3CA的患者相比，癌症特异性生存率显著提高（P = 0.044）。随后的生存分析显示，PIK3CA突变是总生存差的重要预后因素[多因素校正风险比（HR）， 3.9；95%置信区间（95% CI）， 1.3-11.8；p =。[17]和癌症特异性生存率（多因素校正HR， 3.6; 95% CI, 1.2-11.0; P = 0.024）。结合以往已发表的研究结果，本研究进一步支持PIK3CA突变在宫颈癌中的临床意义。我们的观察结果表明，靶向pi3激酶/Akt通路的分子抑制剂可能改善PIK3CA突变宫颈癌的CCRT预后，为基于精准医学的新型治疗策略提供重要意义。
The standard treatment for locally advanced cervical cancer is cisplatin-based concurrent chemoradiotherapy (CCRT). Although the activated PI3-kinase/Akt pathway is known to be involved in both cisplatin-resistance and radioresistance, to date, only a few studies have reported significant associations between PIK3CA gene mutational status and outcome by CCRT in the disease. The aim of this study was to clarify the prognostic significance of PIK3CA mutational status in cervical cancers treated by CCRT. We analyzed PIK3CA mutation in 59 patients with stage IIB to IVA cervical carcinomas primarily treated by CCRT with weekly cisplatin using formalin-fixed paraffin-embedded biopsy specimens before treatment. Fifty-seven of 59 patients (97%) had locally advanced cancers with stage IIIA to IVA. Clinicopathologic data and patient survival were retrospectively compared according to PIK3CA mutational status. PIK3CA mutation was found in 7 of 59 patients (12%). No significant differences in clinicopathologic characteristics were observed according to PIK3CA mutational status. Patients with wild-type PIK3CA showed significantly improved cancer-specific survival as compared with mutated patients (P = .044). Subsequent survival analyses revealed that PIK3CA mutation was a significant prognostic factor for poor overall survival [multivariate adjusted hazard ratio (HR), 3.9; 95% confidence interval (95% CI), 1.3–11.8; P = .017] and cancer-specific survival (multivariate adjusted HR, 3.6; 95% CI, 1.2–11.0; P = .024). Together with previous published findings, the current study further supports the clinical significance of PIK3CA mutation in cervical cancer. Our observations suggest that molecular inhibitors targeting the PI3-kinase/Akt pathway may improve the outcome by CCRT in cervical cancers harboring PIK3CA mutation, providing significant implications for novel treatment strategy based on precision medicine in the disease.