Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Precision Oncology Hub, Tom Baker Cancer Centre, Department of Oncology, University of Calgary, Calgary, AB, Canada.
Gynecol Oncol. 2020 Sep;158(3):776-784. doi: 10.1016/j.ygyno.2020.06.506. Epub 2020 Jul 9.
This study aimed to describe the prognostic value of PI3K/AKT pathway mutations in a large cohort of patients with cervical cancer.
Patients with pre-treatment archival specimens, diagnosed with FIGO stages IB-IVA cervical cancer between 1998 and 2014 and treated with radical, curative intent chemoradiotherapy (CRT) at a single center were identified. Mutational status was determined by next generation sequencing and PIK3CA copy number (CNV) was assessed by digital PCR.
190 patients with available pre-treatment tumor specimens were identified. Median OS and PFS were 57.4 and 46.0 months, respectively. A total of 161 tumors were successfully sequenced; 60 (37.3%) had PI3K/AKT pathway mutations, with 50 (30.1%) having PIK3CA hotspot mutations. PIK3CA CNV gain was noted in 79 (59.2%) of the 154 successfully analyzed. On univariate analysis, PIK3CA mutation was associated with poor OS (HR 1.73; 95% CI: 1.03-2.92; p = .037) but not PFS (HR 1.38; 0.84-2.28; p = .204). Absence of any PI3K/AKT pathway mutation was associated with improved OS (HR 1.68; 1.01-2.81; p = .046) but not PFS (HR 1.50; 0.93-2.43; p = .202). Associations were not maintained when adjusting for clinical factors. On univariate analysis, PIK3CA mutation positive, CNV normal tumors were associated with poorer OS (HR 2.55; 1.18-5.50; p = .017) and trend to worse PFS (HR 1.87; 0.90-3.83; p = .094) when compared to those with CNV gain and wildtype PIK3CA.
PI3K/AKT pathway mutations are common in cervical cancer. Consideration of PIK3CA mutational status with CNV status may be important in predicting outcome in cervical cancer patients.
本研究旨在描述 PI3K/AKT 通路突变在大量宫颈癌患者中的预后价值。
本研究纳入了 1998 年至 2014 年间在单一中心接受根治性、有治愈意图的放化疗（CRT）治疗的 FIGO 分期 IB-IVA 宫颈癌患者，这些患者均有治疗前的存档标本。通过下一代测序确定突变状态，并通过数字 PCR 评估 PIK3CA 拷贝数（CNV）。
共确定了 190 例有可用治疗前肿瘤标本的患者。中位 OS 和 PFS 分别为 57.4 和 46.0 个月。共有 161 例肿瘤成功测序，其中 60 例（37.3%）存在 PI3K/AKT 通路突变，50 例（30.1%）存在 PIK3CA 热点突变。在 154 例成功分析的肿瘤中，79 例（59.2%）存在 PIK3CA CNV 增益。单因素分析显示，PIK3CA 突变与 OS 不良相关（HR 1.73；95%CI：1.03-2.92；p=0.037），但与 PFS 无关（HR 1.38；0.84-2.28；p=0.204）。不存在任何 PI3K/AKT 通路突变与 OS 改善相关（HR 1.68；1.01-2.81；p=0.046），但与 PFS 无关（HR 1.50；0.93-2.43；p=0.202）。当调整临床因素后，这些关联不再成立。单因素分析显示，PIK3CA 突变阳性、CNV 正常的肿瘤与 OS 不良相关（HR 2.55；1.18-5.50；p=0.017），且 PFS 趋势较差（HR 1.87；0.90-3.83；p=0.094），与 CNV 增益和 PIK3CA 野生型相比。
PI3K/AKT 通路突变在宫颈癌中很常见。考虑 PIK3CA 突变状态与 CNV 状态可能对预测宫颈癌患者的预后很重要。
